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Numéro de publicationUS8877035 B2
Type de publicationOctroi
Numéro de demandeUS 13/852,758
Date de publication4 nov. 2014
Date de dépôt28 mars 2013
Date de priorité20 juil. 2005
Autre référence de publicationCA2609720A1, CA2609720C, CA2890945A1, CA2890945C, CA2941312A1, CN103558284A, EP1913374A1, US8425757, US20080173552, US20130256156, WO2007013915A1
Numéro de publication13852758, 852758, US 8877035 B2, US 8877035B2, US-B2-8877035, US8877035 B2, US8877035B2
InventeursHuan-Ping Wu, Christine D. Nelson, Greg P. Beer
Cessionnaire d'origineBayer Healthcare Llc
Exporter la citationBiBTeX, EndNote, RefMan
Liens externes: USPTO, Cession USPTO, Espacenet
Gated amperometry methods
US 8877035 B2
Résumé
A sensor system, device, and methods for determining the concentration of an analyte in a sample is described. Gated amperometric pulse sequences including multiple duty cycles of sequential excitations and relaxations may provide a shorter analysis time and/or improve the accuracy and/or precision of the analysis. The disclosed gated amperometric pulse sequences may reduce analysis errors arising from the hematocrit effect, variance in cap-gap volumes, non-steady-state conditions, mediator background, under-fill, temperature changes in the sample, and a single set of calibration constants.
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The invention claimed is:
1. A method of reducing bias attributable to mediator background in a determined concentration of an analyte in a sample comprising:
generating a measurable species from a mediator, the concentration of the measurable species responsive to a concentration of an analyte in a sample;
applying an input signal to the sample, the input signal comprising at least 3 duty cycles within 180 seconds and each duty cycle comprising an excitation and a relaxation,
where the input signal has a redox intensity of at least 0.01 if continued for a 10 second duration,
where the relaxations of the at least 3 duty cycles each provide an independent diffusion and analyte reaction time during which the analyte generates the measurable species;
measuring an output signal from at least one amperometric excitation of the at least 3 duty cycles,
the output signal responsive to the concentration of the measurable species in the sample, and
the at least one amperometric excitation having a duration from 0.01 second to 1.5 seconds; and
determining the concentration of the analyte in the sample having reduced bias attributable to mediator background in response to the measured output signal, where the determined concentration is responsive to a rate at which the measurable species is oxidized or reduced by the input signal.
2. The method of claim 1, where the sample includes red blood cells.
3. The method of claim 1, where the measurable species is an oxidized or a reduced mediator, the mediator selected from the group consisting of organotransition metal complexes, coordination complexes, electro-active organic molecules, and combinations thereof.
4. The method of claim 1, the input signal comprising from 4 to 8 duty cycles within 3 to 16 seconds.
5. The method of claim 1, the input signal comprising from 3 to 18 duty cycles within 30 seconds.
6. The method of claim 1, where the input signal further comprises a terminal read pulse.
7. The method of claim 1, comprising measuring the output signal of the at least one amperometric excitation having a duration from 0.1 to 1.2 seconds.
8. The method of claim 1, where the excitations of the at least 3 duty cycles each have a duration in the range of 0.1 second through 1.5 second and the at least 3 duty cycles have a pulse interval in the range of about 0.2 second through about 3.5 seconds.
9. The method of claim 1, where the excitations of the at least 3 duty cycles each have a duration in the range of about 0.4 second through about 1.2 second and the at least 3 duty cycles have a pulse interval in the range of about 0.6 second through about 3.7 seconds.
10. The method of claim 1, where at least one of the relaxations of the at least 3 duty cycles has a duration from 0.1 second to 3 seconds and includes a current reduction to at least one-half the current flow of the excitations.
11. The method of claim 1, where at least one of the relaxations of the at least 3 duty cycles is responsive to an open circuit.
12. The method of claim 1, where the measured output signal includes the greatest last in time current value obtained from the excitations of the at least 3 duty cycles.
13. The method of claim 1, further comprising recording the output signal from the at least one amperometric excitation as a function of time.
14. The method of claim 1, further comprising:
determining a current profile from the output signal, where
the determining the concentration of the analyte in the sample having the reduced bias attributable to mediator background in response to the output signal further comprises determining the concentration of the analyte in the sample from the current profile.
15. The method of claim 14, where the analyte concentration of the sample is determined from a portion of the current profile when a relatively constant diffusion rate of the measurable species is reached.
16. The method of claim 14, where the current profile includes a transient decay and the analyte concentration of the sample is determined from a portion of the current profile including the transient decay.
17. The method of claim 1, further comprising previously determining multiple sets of calibration constants in response to the output signal.
18. The method of claim 17, where the multiple sets of calibration constants were determined by taking a current value at a fixed time from each of the excitations of the at least 3 duty cycles after applying the excitations to the sample.
19. The method of claim 17, further comprising:
determining multiple concentrations of the analyte in the sample in response to the multiple sets of calibration constants; and
averaging the multiple concentrations of the analyte in the sample to determine the concentration of the analyte in the sample.
20. The method of claim 1, where the concentration of the analyte in the sample is determined within 4 seconds of applying the input signal to the sample.
21. The method of claim 1, further comprising:
exciting the measurable species internal to a diffusion barrier layer having an average initial thickness from 1 to 30 micrometers, the diffusion barrier layer including a polymeric binder layer that is partially water-soluble; and
substantially excluding from excitation the measurable species external to the diffusion barrier layer, where the diffusion barrier layer provides an internal porous space to contain and isolate a portion of the measurable species from the sample.
22. The method of claim 1, further comprising:
introducing the sample to a sensor strip, the sensor strip including working and counter electrodes in electrical communication with the sample and the mediator;
transferring at least one electron from the analyte in the sample to the mediator or transferring at least one electron to the analyte in the sample from the mediator; and
applying the input signal to the working and counter electrodes, where the input signal electrochemically excites the measurable species.
23. The method of claim 22, where the transferring the at least one electron from the analyte chemically oxidizes the analyte.
24. The method of claim 22, where the transferring the at least one electron to the analyte chemically reduces the analyte.
25. The method of claim 22, further comprising filling a cap-gap of the sensor strip with the sample while expelling previously contained air through a vent before applying the input signal to the sample.
26. The method of claim 22, where the working and the counter electrodes are in substantially the same plane.
27. A method of signaling a user to add additional sample to a sensor strip, comprising:
applying an input signal to a sample contacting working and counter electrodes of a sensor strip, the input signal including at least 3 duty cycles within 180 seconds and each duty cycle comprising an excitation and a relaxation;
measuring an output signal including currents from the excitations of at least two of the at least 3 duty cycles;
determining a decay constant profile from the measured output signal for the at least two excitations;
determining if the sensor strip is under-filled from the decay constant profiles determined from the at least two excitations;
signaling the user to add additional sample to the sensor strip when the sensor strip is under-filled; and
determining a concentration of an analyte in the sample from the output signal.
28. The method of claim 27, further comprising recording the currents as a transient current profile for each of the at least two excitations.
29. The method of claim 28, further comprising determining contour profiles of decay rate as a function of time from the transient current profile for each of the at least two excitations.
30. The method of claim 29, further comprising converting the contour profiles of decay rate as a function of time to the decay constant profile with a K constant of a decay process.
31. The method of claim 27, where the user is signaled to add the additional sample to the sensor strip when an actual decay constant of the current profile is less than a selected value.
32. The method of claim 27, where the user is signaled to add the additional sample to the sensor strip within 3 to 5 seconds of applying the input signal to the sample contacting the working and the counter electrodes.
33. A method of determining the temperature of a sample contained by a sensor strip, comprising:
previously determining correlations between decay rate and temperature;
determining a current profile from currents recorded during at least two excitations of an input signal including at least 3 duty cycles within 180 seconds;
correlating the current profile to the correlations between decay rate and temperature to determine the temperature of the sample.
34. The method of claim 33, where the current profile of at least one of the at least two excitations is expressed as a K constant.
35. The method of claim 33, further comprising generating a contour profile from the current profile of the at least two excitations.
36. The method of claim 33, where the current profile is transient.
37. The method of claim 33, further comprising determining an analyte concentration of the sample from the currents recorded from the input signal in response to the determined temperature of the sample.
38. A method of determining the duration of an input signal to apply to a sample, for determining the concentration of an analyte in the sample, the method comprising:
previously determining multiple sets of calibration constants from currents recorded at fixed times from an output signal;
applying an input signal including at least 3 duty cycles within 180 seconds to the sample, where each of the at least 3 duty cycles includes an excitation; and
determining a concentration of the analyte in the sample from an output signal measured from the excitation of at least one of the at least 3 duty cycles;
determining the duration of the input signal to apply to the sample in response to the determined concentration of the analyte in the sample.
39. The method of claim 38, where the multiple sets of calibration constants are determined from current values recorded at a fixed time after applying the excitation for the at least 3 duty cycles.
40. The method of claim 38, further comprising determining a current profile from currents recorded from the excitations of the at least 3 duty cycles within 180 seconds.
41. The method of claim 40, where the currents are transient.
42. The method of claim 40, further comprising generating a contour profile from the current profile of the at least 3 duty cycles.
43. The method of claim 42, where the determined concentration of the analyte in the sample is determined from the highest current value of the contour profile, and where the determined concentration of the analyte in the sample is used to determine the duration of the input signal to apply to the sample.
44. The method of claim 38, where the duration of the input signal is determined in terms of the number of duty cycles applied to the sample.
45. The method of claim 43, where the duration of the input signal is determined in terms of the number of duty cycles applied to the sample.
46. The method of claim 44, where the number of duty cycles in the input signal is determined in response to the multiple sets of calibration constants and the determined concentration of the analyte in the sample.
47. The method of claim 45, where the number of duty cycles in the input signal is determined in response to the multiple sets of calibration constants and the determined concentration of the analyte in the sample.
48. The method of claim 38, where a high determined concentration of the analyte in the sample provides a shorter duration of the input signal than when a low determined concentration of the analyte in the sample is determined.
49. The method of claim 44, where a high determined concentration of the analyte in the sample provides a shorter duration of the input signal than when a low determined concentration of the analyte in the sample is determined.
50. A handheld measuring device, for determining the concentration of an analyte in a sample, where
the device is capable of receiving a sensor strip and the device comprises:
contacts;
at least one display; and
electrical circuitry establishing electrical communication between the contacts and the display, the circuitry comprising:
an electric charger and a processor in electrical communication, the processor in electrical communication with a non-transitory computer readable storage medium comprising computer readable software code, which when executed by the processor, the processor is capable of causing the charger to implement an input signal comprising at least 3 duty cycles within 180 seconds between the contacts, each duty cycle comprising an excitation and a relaxation; where
the input signal has a redox intensity of at least 0.01 if continued for a 10 second duration of the input signal;
the processor is capable of measuring the output signal from an amperometric excitation of the at least 3 duty cycles, the amperometric excitation having a duration from 0.01 to 1.5 seconds, where
the amperometric excitation follows a relaxation providing an independent diffusion and analyte reaction time during which the analyte generates measurable species, the relaxation provided by an open circuit; and
the processor is capable of determining an analyte concentration of a sample from the measured output signal, where the determined concentration is responsive to a rate at which the measurable species is oxidized or reduced by the input signal.
51. The device of claim 50, where the sample includes red blood cells.
52. The device of claim 50, where the processor is further capable of measuring at least one current profile at the contacts and determining the concentration of the analyte in the sample in response to the at least one current profile.
53. The device of claim 52, where the at least one current profile includes transient currents.
54. The device of claim 50, where the processor is further capable of causing the charger to implement the input signal in response to a sample providing electron flow between the contacts.
55. The device of claim 50, where the processor is further capable of determining when the measured output signal is a greatest last in time current value obtained from the amperometric excitation having the duration from 0.01 to 1.5 seconds.
56. The device of claim 50, where the charger is a charger-recorder and the processor is capable of measuring the output signal from the recorder.
57. The device of claim 50, where the charger and the processor are capable of determining the concentration of the analyte in the sample within 4 seconds of the charger applying the input signal between the contacts.
Description
REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No. 11/960,062 entitled “Gated Amperometry” filed Dec. 19, 2007, which is a continuation of PCT/US2006/028013 entitled “Gated Amperometry” filed Jul. 19, 2006, which was published in English and claimed the benefit of U.S. Provisional Application No. 60/700,787 entitled “Gated Amperometry” as filed on Jul. 20, 2005, and U.S. Provisional Application No. 60/746,771 entitled “Abnormal Output Detection System for a Biosensor” as filed on May 8, 2006, each of which are incorporated herein by reference.

BACKGROUND

The quantitative determination of analytes in biological fluids is useful in the diagnosis and treatment of physiological abnormalities. For example, determining the glucose level in biological fluids, such as blood, is important to diabetic individuals who must frequently check their blood glucose level to regulate their diets and/or medication.

Electrochemical systems have been used for this type of analysis. During the analysis, the analyte undergoes a redox reaction with an enzyme or similar species to generate an electric current that may be measured and correlated with the concentration of the analyte. A substantial benefit may be provided to the user by decreasing the time required for the analysis while supplying the desired accuracy and precision.

One example of an electrochemical sensor system for analyzing analytes in biological fluids includes a measuring device and a sensor strip. The sensor strip includes reagents to react with and transfer electrons from the analyte during the analysis and electrodes to pass the electrons through conductors that connect the strip with the device. The measuring device includes contacts to receive the electrons from the strip and the ability to apply a voltage differential between the contacts. The device may record the current passing through the sensor and translate the current values into a measure of the analyte content of the sample. These sensor systems may analyze a single drop of whole blood (WB), such as from 1-15 microliters (μL) in volume.

Examples of bench-top measuring devices include the BAS 100B Analyzer available from BAS Instruments in West Lafayette, Ind.; the CH Instrument Analyzer available from CH Instruments in Austin, Tex.; the Cypress Electrochemical Workstation available from Cypress Systems in Lawrence, Kans.; and the EG&G Electrochemical Instrument available from Princeton Research Instruments in Princeton, N.J. Examples of portable measuring devices include the Ascensia Breeze® and Elite® meters of Bayer Corporation.

The sensor strip may include a working electrode where the analyte undergoes electrochemical reaction and a counter electrode where the opposite electrochemical reaction occurs, thus allowing current to flow between the electrodes. Thus, if oxidation occurs at the working electrode, reduction occurs at the counter electrode. See, for example, Fundamentals Of Analytical Chemistry, 4th Edition, D. A. Skoog and D. M. West; Philadelphia: Saunders College Publishing (1982), pp 304-341.

The sensor strip also may include a true reference electrode to provide a non-variant reference potential to the measuring device. While multiple reference electrode materials are known, a mixture of silver (Ag) and silver chloride (AgCl) is typical due to the insolubility of the mixture in the aqueous environment of the analysis solution. A reference electrode also may be used as the counter electrode. A sensor strip using such a combination reference-counter electrode is described in U.S. Pat. No. 5,820,551.

The sensor strip may be formed by printing electrodes on an insulating substrate using multiple techniques, such as those described in U.S. Pat. Nos. 6,531,040; 5,798,031; and 5,120,420. One or more reagent layer may be formed by coating one or more of the electrodes, such as the working and/or counter electrodes. In one aspect, more than one of the electrodes may be covered by the same reagent layer, such as when the working and counter electrodes are coated by the same composition. In another aspect, reagent layers having different compositions may be printed or micro-deposited onto the working and counter electrodes using the method described in a U.S. provisional patent application filed Oct. 24, 2003, Application No. 60/513,817. Thus, the reagent layer on the working electrode may contain the enzyme, the mediator, and a binder while the reagent layer on the counter electrode contains a soluble redox species, which could be the same as the mediator or different, and a binder.

The reagent layer may include an ionizing agent for facilitating the oxidation or reduction of the analyte, as well as any mediators or other substances that assist in transferring electrons between the analyte and the conductor. The ionizing agent may be an analyte specific enzyme, such as glucose oxidase or glucose dehydrogenase, to catalyze the oxidation of glucose in a whole blood (WB) sample. The reagent layer also may include a binder that holds the enzyme and mediator together. Table I, below, provides conventional combinations of enzymes and mediators for use with specific analytes.

TABLE I
Analyte Enzyme Mediator
Glucose Glucose Oxidase Ferricyanide
Glucose Glucose Dehydrogenase Ferricyanide
Cholesterol Cholesterol Oxidase Ferricyanide
Lactate Lactate Oxidase Ferricyanide
Uric Acid Uricase Ferricyanide
Alcohol Alcohol Oxidase Phenylenediamine

The binder may include various types and molecular weights of polymers, such as CMC (carboxylmethyl cellulose) and/or PEO (polyethylene oxide). In addition to binding the reagents together, the binder may assist in filtering red blood cells, preventing them from coating the electrode surface.

Examples of conventional electrochemical sensor systems for analyzing analytes in biological fluids include the Precision® biosensors available from Abbott in Abbott Park, Ill.; Accucheck® biosensors available from Roche in Indianapolis, Ind.; and OneTouch Ultra® biosensors available from Lifescan in Milpitas, Calif.

One electrochemical method, which has been used to quantify analytes in biological fluids, is coulometry. For example, Heller et al. described the coulometric method for whole blood glucose measurements in U.S. Pat. No. 6,120,676. In coulometry, the analyte concentration is quantified by exhaustively oxidizing the analyte within a small volume and integrating the current over the time of oxidation to produce the electrical charge representing the analyte concentration. In other words, coulometry captures the total amount of glucose within the sensor strip.

An important aspect of coulometry is that towards the end of the integration curve of charge vs. time, the rate at which the current changes with time becomes substantially constant to yield a steady-state condition. This steady-state portion of the coulometric curve forms a relatively flat plateau region, thus allowing determination of the corresponding current. However, the coulometric method requires the complete conversion of the entire volume of analyte to reach the steady-state condition. As a result, this method is time consuming and does not provide the fast results which users of electrochemical devices, such as glucose-monitoring products, demand. Another problem with coulometry is that the small volume of the sensor cell must be controlled in order to provide accurate results, which can be difficult with a mass produced device.

Another electrochemical method which has been used to quantify analytes in biological fluids is amperometry. In amperometry, current is measured during a read pulse as a constant potential (voltage) is applied across the working and counter electrodes of the sensor strip. The measured current is used to quantify the analyte in the sample. Amperometry measures the rate at which the electrochemically active species, and thus the analyte, is being oxidized or reduced near the working electrode. Many variations of the amperometric method for biosensors have been described, for example in U.S. Pat. Nos. 5,620,579; 5,653,863; 6,153,069; and 6,413,411.

A disadvantage of conventional amperometric methods is the non-steady-state nature of the current after a potential is applied. The rate of current change with respect to time is very fast initially and becomes slower as the analysis proceeds due to the changing nature of the underlying diffusion process. Until the consumption rate of the reduced mediator at the electrode surface equals the diffusion rate, a steady-state current cannot be obtained. Thus, for amperometry methods, measuring the current during the transient period before a steady-state condition is reached may be associated with more inaccuracy than a measurement taken during a steady-state time period.

The “hematocrit effect” provides an impediment to accurately analyzing the concentration of glucose in WB samples. WB samples contain red blood (RB) cells and plasma. The plasma is mostly water, but contains some proteins and glucose. Hematocrit is the volume of the RB cell constituent in relation to the total volume of the WB sample and is often expressed as a percentage. Whole blood samples generally have hematocrit percentages ranging from 20% to 60%, with ˜40% being the average.

In conventional sensor strips for determining glucose concentrations, glucose may be oxidized by an enzyme, which then transfers the electron to a mediator. This reduced mediator then travels to the working electrode where it is electrochemically oxidized. The amount of mediator being oxidized may be correlated to the current flowing between the working and counter electrodes of the sensor strip. Quantitatively, the current measured at the working electrode is directly proportional to the diffusion coefficient of the mediator. The hematocrit effect interferes with this process because the RB cells block the diffusion of the mediator to the working electrode. Subsequently, the hematocrit effect influences the amount of current measured at the working electrode without any connection to the amount of glucose in the sample.

WB samples having varying concentrations of RB cells may cause inaccuracies in the measurement because the sensor may not distinguish between a lower mediator concentration and a higher mediator concentration where the RB cells block diffusion to the working electrode. For example, when WB samples containing identical glucose levels, but having hematocrits of 20, 40, and 60%, are analyzed, three different glucose readings will be reported by a conventional sensor system based on one set of calibration constants (slope and intercept, for instance). Even though the glucose concentrations are the same, the system will report that the 20% hematocrit sample contains more glucose than the 60% hematocrit sample due to the RB cells interfering with diffusion of the mediator to the working electrode.

The normal hematocrit range (RBC concentration) for humans is from 20% to 60% and is centered around 40%. Hematocrit bias refers to the difference between the reference glucose concentration obtained with a reference instrument, such as the YSI 2300 STAT PLUS™ available from YSI Inc., Yellow Springs, Ohio, and an experimental glucose reading obtained from a portable sensor system for samples containing differing hematocrit levels. The difference between the reference and experimental readings results from the varying hematocrit levels between specific whole blood samples.

In addition to the hematocrit effect, measurement inaccuracies also may arise when the measurable species concentration does not correlate with the analyte concentration. For example, when a sensor system determines the concentration of a reduced mediator generated in response to the oxidation of an analyte, any reduced mediator not generated by oxidation of the analyte will lead to the sensor system indicating that more analyte is present in the sample than is correct due to mediator background.

In addition to the hematocrit and mediator background effects, other factors also may lead to inaccuracies in the ability of a conventional electrochemical sensor system to determine the concentration of an analyte in a sample. In one aspect, these inaccuracies may be introduced because the portion of the sensor strip that contains the sample may vary in volume from strip to strip. Inaccuracies also may be introduced when sufficient sample is not provided to completely fill the volume of the cap-gap, a condition referred to as under-fill. In other aspects, inaccuracies may be introduced into the measurement by random “noise” and when the sensor system lacks the ability to accurately determine temperature changes in the sample.

In an attempt to overcome one or more of these disadvantages, conventional sensor systems have attempted multiple techniques, not only with regard to the mechanical design of the sensor strip and reagent selection, but also regarding the manner in which the measuring device applies the electric potential to the strip. For example, conventional methods of reducing the hematocrit effect for amperometric sensors include the use of filters, as disclosed in U.S. Pat. Nos. 5,708,247 and 5,951,836; reversing the polarity of the applied current, as disclosed in WO 01/57510; and by methods that maximize the inherent resistance of the sample, as disclosed in U.S. Pat. No. 5,628,890.

Multiple methods of applying the electric potential to the strip, commonly referred to as pulse methods, sequences, or cycles, have been used to address inaccuracies in the determined analyte concentration. For example, in U.S. Pat. No. 4,897,162 the pulse method includes a continuous application of rising and falling voltage potentials that are commingled to give a triangular-shaped wave. Furthermore, WO 2004/053476 and U.S. Publication Nos. 2003/0178322 and 2003/0113933 describe pulse methods that include the continuous application of rising and falling voltage potentials that also change polarity.

Other conventional methods combine a specific electrode configuration with a pulse sequence adapted to that configuration. For example, U.S. Pat. No. 5,942,102 combines the specific electrode configuration provided by a thin layer cell with a continuous pulse so that the reaction products from the counter electrode arrive at the working electrode. This combination is used to drive the reaction until the current change verses time becomes constant, thus reaching a true steady state condition for the mediator moving between the working and counter electrodes during the potential step. While each of these methods balances various advantages and disadvantages, none are ideal.

As may be seen from the above description, there is an ongoing need for improved electrochemical sensor systems, especially those that may provide increasingly accurate determination of the analyte concentration in less time. The systems, devices, and methods of the present invention overcome at least one of the disadvantages associated with conventional systems.

SUMMARY

A method of determining the concentration of an analyte in a sample is provided that includes applying a pulse sequence to the sample, the pulse sequence including at least 3 duty cycles within 180 seconds. The duty cycles may each include an excitation at a fixed potential, during which a current may be recorded, and a relaxation. The pulse sequence may include a terminal read pulse and may be applied to a sensor strip including a diffusion barrier layer (DBL) on a working electrode. The determined analyte concentration may include less bias attributable to mediator background than the same or another method lacking the pulse sequence including at least 3 duty cycles within 180 seconds. Through the use of transient current data, the concentration of the analyte may be determined when a steady-state condition is not reached during the excitation portions of the duty cycles of the pulse sequence. A data treatment may be applied to the measured currents to determine the concentration of the analyte in the sample.

A handheld analyte measuring device is provided for determining the concentration of an analyte in a sample. The device includes a gated amperometric measuring device adapted to receive a sensor strip. The gated amperometric measuring device includes at least two device contacts in electrical communication with a display through electrical circuitry. The sensor strip includes at least first and second sensor strip contacts. The first sensor strip contact is in electrical communication with a working electrode and the second sensor strip contact is in electrical communication with a counter electrode through conductors. A first reagent layer is on at least one of the electrodes and includes an oxidoreductase and at least one species of a redox pair.

A handheld measuring device adapted to receive a sensor strip is provided for determining the concentration of an analyte in a sample. The device includes contacts, at least one display, and electronic circuitry establishing electrical communication between the contacts and the display. The circuitry includes an electric charger and a processor, where the processor is in electrical communication with a computer readable storage medium. The medium includes computer readable software code, which when executed by the processor, causes the charger to implement a pulse sequence comprising at least 3 duty cycles within 180 seconds between the contacts.

A method of reducing the bias attributable to mediator background in a determined concentration of an analyte in a sample is provided that includes applying a pulse sequence including at least 3 duty cycles within 180 seconds to the sample.

A method of determining the duration of a pulse sequence including at least 3 duty cycles within 180 seconds, for determining the concentration of an analyte in a sample is provided that includes determining a plurality of sets of calibration constants determined from currents recorded during the at least 3 duty cycles and determining the duration of the pulse sequence in response to the determined concentration of the analyte in the sample.

A method of signaling a user to add additional sample to a sensor strip is provided that includes determining if the sensor strip is under-filled by determining a decay constant from currents recorded during a gated amperometric pulse sequence and signaling the user to add additional sample to the sensor strip if the strip is under-filled.

A method of determining the temperature of a sample contained by a sensor strip is provided that includes determining a decay constant from currents recorded during a gated amperometric pulse sequence and correlating the decay constant with a temperature value.

A method of determining the duration of a pulse sequence for determining the concentration of an analyte in a sample is provided that includes determining the temperature of a sample contained by a sensor strip from decay constants determined from currents recorded during a gated amperometric pulse sequence.

The following definitions are included to provide a clear and consistent understanding of the specification and claims.

The term “analyte” is defined as one or more substances present in a sample. The analysis determines the presence and/or concentration of the analyte present in the sample.

The term “sample” is defined as a composition that may contain an unknown amount of the analyte. Typically, a sample for electrochemical analysis is in liquid form, and preferably the sample is an aqueous mixture. A sample may be a biological sample, such as blood, urine, or saliva. A sample also may be a derivative of a biological sample, such as an extract, a dilution, a filtrate, or a reconstituted precipitate.

The term “measurable species” is defined as any electrochemically active species that may be oxidized or reduced under an appropriate potential at the working electrode of an electrochemical sensor strip. Examples of measurable species include analytes, oxidoreductases, and mediators.

The term “amperometry” is defined as an analysis method where the concentration of an analyte in a sample is determined by electrochemically measuring the oxidation or reduction rate of the analyte at a potential.

The term “system” or “sensor system” is defined as a sensor strip in electrical communication through its conductors with a measuring device, which allows for the quantification of an analyte in a sample.

The term “sensor strip” is defined as a device that contains the sample during the analysis and provides electrical communication between the sample and the measuring device. The portion of the sensor strip that contains the sample is often referred to as the “cap-gap.”

The term “conductor” is defined as an electrically conductive substance that remains stationary during an electrochemical analysis.

The term “measuring device” is defined as one or more electronic devices that may apply an electric potential to the conductors of a sensor strip and measure the resulting current. The measuring device also may include the processing capability to determine the presence and/or concentration of one or more analytes in response to the recorded current values.

The term “accuracy” is defined as how close the amount of analyte measured by a sensor strip corresponds to the true amount of analyte in the sample. In one aspect, accuracy may be expressed in terms of bias.

The term “precision” is defined as how close multiple analyte measurements are for the same sample. In one aspect, precision may be expressed in terms of the spread or variance among multiple measurements.

The term “redox reaction” is defined as a chemical reaction between two species involving the transfer of at least one electron from a first species to a second species. Thus, a redox reaction includes an oxidation and a reduction. The oxidation half-cell of the reaction involves the loss of at least one electron by the first species, while the reduction half-cell involves the addition of at least one electron to the second species. The ionic charge of a species that is oxidized is made more positive by an amount equal to the number of electrons removed. Likewise, the ionic charge of a species that is reduced is made less positive by an amount equal to the number of electrons gained.

The term “mediator” is defined as a substance that may be oxidized or reduced and that may transfer one or more electrons. A mediator is a reagent in an electrochemical analysis and is not the analyte of interest, but provides for the indirect measurement of the analyte. In a simplistic system, the mediator undergoes a redox reaction in response to the oxidation or reduction of the analyte. The oxidized or reduced mediator then undergoes the opposite reaction at the working electrode of the sensor strip and is regenerated to its original oxidation number.

The term “binder” is defined as a material that provides physical support and containment to the reagents while having chemical compatibility with the reagents.

The term “mediator background” is defined as the bias introduced into the measured analyte concentration attributable to measurable species not responsive to the underlying analyte concentration.

The term “under-fill” is defined as when insufficient sample was introduced into the sensor strip to obtain an accurate analysis.

The term “redox pair” is defined as two conjugate species of a chemical substance having different oxidation numbers. Reduction of the species having the higher oxidation number produces the species having the lower oxidation number. Alternatively, oxidation of the species having the lower oxidation number produces the species having the higher oxidation number.

The term “oxidation number” is defined as the formal ionic charge of a chemical species, such as an atom. A higher oxidation number, such as (III), is more positive, and a lower oxidation number, such as (II), is less positive.

The term “soluble redox species” is defined as a substance that is capable of undergoing oxidation or reduction and that is soluble in water (pH 7, 25° C.) at a level of at least 1.0 grams per Liter. Soluble redox species include electro-active organic molecules, organotransition metal complexes, and transition metal coordination complexes. The term “soluble redox species” excludes elemental metals and lone metal ions, especially those that are insoluble or sparingly soluble in water.

The term “oxidoreductase” is defined as any enzyme that facilitates the oxidation or reduction of an analyte. An oxidoreductase is a reagent. The term oxidoreductase includes “oxidases,” which facilitate oxidation reactions where molecular oxygen is the electron acceptor; “reductases,” which facilitate reduction reactions where the analyte is reduced and molecular oxygen is not the analyte; and “dehydrogenases,” which facilitate oxidation reactions where molecular oxygen is not the electron acceptor. See, for example, Oxford Dictionary of Biochemistry and Molecular Biology, Revised Edition, A. D. Smith, Ed., New York: Oxford University Press (1997) pp. 161, 476, 477, and 560.

The term “electro-active organic molecule” is defined as an organic molecule lacking a metal that is capable of undergoing an oxidation or reduction reaction. Electro-active organic molecules may serve as mediators.

The term “organotransition metal complex,” also referred to as “OTM complex,” is defined as a complex where a transition metal is bonded to at least one carbon atom through a sigma bond (formal charge of −1 on the carbon atom sigma bonded to the transition metal) or a pi bond (formal charge of 0 on the carbon atoms pi bonded to the transition metal). For example, ferrocene is an OTM complex with two cyclopentadienyl (Cp) rings, each bonded through its five carbon atoms to an iron center by two pi bonds and one sigma bond. Another example of an OTM complex is ferricyanide (III) and its reduced ferrocyanide (II) counterpart, where six cyano ligands (formal charge of −1 on each of the 6 ligands) are sigma bonded to an iron center through the carbon atoms.

The term “coordination complex” is defined as a complex having well-defined coordination geometry, such as octahedral or square planar. Unlike OTM complexes, which are defined by their bonding, coordination complexes are defined by their geometry. Thus, coordination complexes may be OTM complexes (such as the previously mentioned ferricyanide), or complexes where non-metal atoms other than carbon, such as heteroatoms including nitrogen, sulfur, oxygen, and phosphorous, are datively bonded to the transition metal center. For example, ruthenium hexaamine is a coordination complex having a well-defined octahedral geometry where six NH3 ligands (formal charge of 0 on each of the 6 ligands) are datively bonded to the ruthenium center. A more complete discussion of organotransition metal complexes, coordination complexes, and transition metal bonding may be found in Collman et al., Principles and Applications of Organotransition Metal Chemistry (1987) and Miessler & Tarr, Inorganic Chemistry (1991).

The term “steady-state” is defined as when the change in electrochemical signal (current) with respect to its independent input variable (voltage or time) is substantially constant, such as within ±10 or ±5%.

The term “transient point” is defined as the current value obtained as a function of time when an increasing rate of diffusion of a measurable species to a conductor surface transitions into a relatively constant rate of diffusion. Before the transient point, the current is rapidly changing with time. Similarly, after the transient point, the rate of current decay becomes relatively constant, thus reflecting the relatively constant rate of diffusion of a measurable species to a conductor surface.

The term “relatively constant” is defined as when the change in a current value or a diffusion rate is within ±20, ±10, or ±5%.

The term “average initial thickness” refers to the average height of a layer prior to the introduction of a liquid sample. The term average is used because the top surface of the layer is uneven, having peaks and valleys.

The term “redox intensity” (RI) is defined as the total excitation time divided by the sum of the total excitation time and the total relaxation time delays for a pulse sequence.

The term “handheld device” is defined as a device that may be held in a human hand and is portable. An example of a handheld device is the measuring device accompanying Ascensia® Elite Blood Glucose Monitoring System, available from Bayer HealthCare, LLC, Tarrytown, N.Y.

The term “on” is defined as “above” and is relative to the orientation being described. For example, if a first element is deposited over at least a portion of a second element, the first element is said to be “deposited on” the second. In another example, if a first element is present above at least a portion of a second element, the first element is said to be “on” the second. The use of the term “on” does not exclude the presence of substances between the upper and lower elements being described. For example, a first element may have a coating over its top surface, yet a second element over at least a portion of the first element and its top coating may be described as “on” the first element. Thus, the use of the term “on” may or may not mean that the two elements being related are in physical contact.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention may be better understood with reference to the following drawings and description. The components in the figures are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. Moreover, in the figures, like referenced numerals designate corresponding parts throughout the different views.

FIG. 1A is a perspective representation of an assembled sensor strip.

FIG. 1B is a top-view diagram of a sensor strip, with the lid removed.

FIG. 2 depicts an end-view diagram of the sensor strip of FIG. 1B.

FIG. 3 represents an electrochemical analytic method of determining the presence and concentration of an analyte in a sample.

FIGS. 4A and 4B depict a working electrode having a surface conductor and a DBL during the application of long and short read pulses.

FIGS. 5A-5E represent five examples of pulse sequences where multiple duty cycles were applied to the sensor strip after introduction of the sample.

FIG. 6A shows the transient output currents of the pulse sequence represented in FIG. 5B for 40% hematocrit WB samples containing 50, 100, 200, 400, and 600 mg/dl glucose.

FIG. 6B shows current contour profiles prepared by plotting and connecting the final current value from each of the transient current profiles shown in FIG. 6A.

FIG. 6C shows current contour profiles prepared from transient current profiles generated by the pulse sequence depicted in FIG. 5E.

FIG. 6D is a graph illustrating output signals in relation to input signals for an electrochemical system using gated amperometric pulse sequences.

FIGS. 7A and 7B are graphs illustrating the improvement in measurement accuracy when a DBL is combined with a short read pulse.

FIGS. 7C and 7D are graphs illustrating the reduction in hematocrit bias that may be obtained when a gated amperometric pulse sequence is combined with a DBL.

FIG. 8 plots the endpoint currents recorded at multiple duty cycles when the pulse sequence of FIG. 5B was applied to WB samples containing various glucose concentrations.

FIG. 9A depicts the transient current profiles obtained from the pulse sequence represented in FIG. 5B when a 2.0 μL sample was introduced to 10 different sensor strips.

FIG. 9B depicts the profiles of the decay rate of each pulse sequence converted from FIG. 9A as a function of time.

FIG. 10 plots K constants determined from a pulse sequence for glucose concentrations of 50, 100, and 400 mg/dL as a function of temperature.

FIG. 11 is a schematic representation of a measuring device.

DETAILED DESCRIPTION

The present invention makes use of the discovery that gated amperometric pulse sequences including multiple duty cycles may provide improved accuracy and precision to an analysis, while reducing the completion time of the analysis. Each duty cycle includes an excitation that may be provided at a relatively constant voltage. Each duty cycle also includes a relaxation that may be provided by an open circuit. The pulse sequences of the present invention may reduce the time required for analysis by eliminating the need for additional delays and pulses, such as “incubation” delays to provide reagent rehydration, “burn-off” pulses to renew the electrodes, and mediator regeneration pulses to renew the oxidation state of the mediator, thus reducing analysis time.

Even with shorter analysis times, the gated amperometric pulse sequences of the present invention may improve accuracy and/or precision in relation to conventional methods. In one aspect, accuracy errors introduced by the hematocrit effect and precision errors introduced by varying cap-gap volume may be reduced through the combination of a diffusion barrier layer with the pulse sequences of the present invention. In another aspect, errors otherwise resulting from a non-steady-state sensor condition and/or mediator background may be reduced. The gated pulse sequences of the present invention also may allow the determination of transient current and contour profiles that simulate a steady-state condition. The transient current profiles may be used to provide a plurality of sets of calibration constants, under-fill detection, and the ability to determine the temperature of the sample, instead of relying on the temperature from the measuring device.

FIGS. 1A and 1B depict a sensor strip 100, which may be used in the present invention. FIG. 1A is a perspective representation of an assembled sensor strip 100 including a sensor base 110, at least partially covered by a lid 120 that includes a vent 130, a concave area 140, and an input end opening 150. A partially-enclosed volume 160 (the cap-gap) is formed between the base 110 and the lid 120. Other sensor strip designs compatible with the present invention also may be used, such as those described in U.S. Pat. Nos. 5,120,420 and 5,798,031.

A liquid sample for analysis may be transferred into the cap-gap 160 by introducing the liquid to the opening 150. The liquid fills the cap-gap 160 while expelling the previously contained air through the vent 130. The cap-gap 160 may contain a composition (not shown) that assists in retaining the liquid sample in the cap-gap. Examples of such compositions include water-swellable polymers, such as carboxymethyl cellulose and polyethylene glycol; and porous polymer matrices, such as dextran and polyacrylamide.

FIG. 1B depicts a top-view of the sensor strip 100, with the lid 120 removed. Conductors 170 and 180 may run under a dielectric layer 190 from the opening 150 to a working electrode 175 and a counter electrode 185, respectively. In one aspect, the working and counter electrodes 175, 185 may be in substantially the same plane, as depicted in the figure. In a related aspect, the working and counter electrodes 175, 185 may be separated by greater than 200 or 250 μm and may be separated from an upper portion of the lid 120 by at least 100 μm. The dielectric layer 190 may partially cover the electrodes 175, 185 and may be made from any suitable dielectric material, such as an insulating polymer.

The counter electrode 185 balances the potential at the working electrode 175 of the sensor strip 100. In one aspect, this potential may be a reference potential achieved by forming the counter electrode 185 from a redox pair, such as Ag/AgCl, to provide a combined reference-counter electrode. In another aspect, the potential may be provided to the sensor system by forming the counter electrode 185 from an inert material, such as carbon, and including a soluble redox species, such as ferricyanide, within the cap-gap 160. Alternatively, the sensor strip 100 may be provided with a third conductor and electrode (not shown) to provide a reference potential to the sensor system.

FIG. 2 depicts an end-view diagram of the sensor strip depicted in FIG. 1B showing the layer structure of the working electrode 175 and the counter electrode 185. The conductors 170 and 180 may lie directly on the base 110. Surface conductor layers 270 and 280 optionally may be deposited on the conductors 170 and 180, respectively. The surface conductor layers 270, 280 may be made from the same or from different materials.

The material or materials used to form the conductors 170, 180 and the surface conductor layers 270, 280 may include any electrical conductor. Preferable electrical conductors are non-ionizing, such that the material does not undergo a net oxidation or a net reduction during analysis of the sample. The conductors 170, 180 preferably include a thin layer of a metal paste or metal, such as gold, silver, platinum, palladium, copper, or tungsten. The surface conductor layers 270, 280 preferably include carbon, gold, platinum, palladium, or combinations thereof. If a surface conductor layer is not present on a conductor, the conductor is preferably made from a non-ionizing material.

The surface conductor material may be deposited on the conductors 170, 180 by any conventional means compatible with the operation of the sensor strip, including foil deposition, chemical vapor deposition, slurry deposition, and the like. In the case of slurry deposition, the mixture may be applied as an ink to the conductors 170, 180, as described in U.S. Pat. No. 5,798,031.

The reagent layers 275 and 285 may be deposited on the conductors 170 and 180, respectively, and include reagents and optionally a binder. The binder material is preferably a polymeric material that is at least partially water-soluble. Suitable partially water-soluble polymeric materials for use as the binder may include poly(ethylene oxide) (PEO), carboxy methyl cellulose (CMC), polyvinyl alcohol (PVA), hydroxyethylene cellulose (HEC), hydroxypropyl cellulose (HPC), methyl cellulose, ethyl cellulose, ethyl hydroxyethyl cellulose, carboxymethyl ethyl cellulose, polyvinyl pyrrolidone (PVP), polyamino acids such as polylysine, polystyrene sulfonate, gelatin, acrylic acid, methacrylic acid, starch, maleic anhydride salts thereof, derivatives thereof, and combinations thereof. Among the above binder materials, PEO, PVA, CMC, and PVA are preferred, with CMC and PEO being more preferred at present.

In addition to the binder, the reagent layers 275 and 285 may include the same or different reagents. In one aspect, the reagents present in the first layer 275 may be selected for use with the working electrode 175, while the reagents present in the second layer 285 may be selected for use with the counter electrode 185. For example, the reagents in the layer 285 may facilitate the free flow of electrons between the sample and the conductor 180. Similarly, the reagents in the layer 275 may facilitate the reaction of the analyte.

The reagent layer 275 may include an oxidoreductase specific to the analyte that may facilitate the reaction of the analyte while enhancing the specificity of the sensor system to the analyte, especially in complex biological samples. Examples of some specific oxidoreductases and corresponding analytes are given below in Table II.

TABLE II
Oxidoreductase (reagent layer) Analyte
Glucose dehydrogenase β-glucose
Glucose oxidase β-glucose
Cholesterol esterase; cholesterol oxidase Cholesterol
Lipoprotein lipase; glycerol kinase; glycerol-3- Triglycerides
phosphate oxidase
Lactate oxidase; lactate dehydrogenase; diaphorase Lactate
Pyruvate oxidase Pyruvate
Alcohol oxidase Alcohol
Bilirubin oxidase Bilirubin
Uricase Uric acid
Glutathione reductase NAD(P)H
Carbon monoxide oxidoreductase Carbon monoxide

At present, especially preferred oxidoreductases for glucose analysis include glucose oxidase, glucose dehydrogenase, derivatives thereof, or combinations thereof.

The reagent layer 275 also may include a mediator to more effectively communicate the results of the analyte reaction to the surface conductor 270 and/or the conductor 170. Examples of mediators include OTM complexes, coordination complexes, and electro-active organic molecules. Specific examples include ferrocene compounds, ferrocyanide, ferricyanide, coenzymes of substituted or unsubstituted pyrroloquinoline quinones (PQQ), substituted or unsubstituted 3-phenylimino-3H-phenothiazines (PIPT), 3-phenylimino-3H-phenoxazine (PIPO), substituted or unsubstituted benzoquinones, substituted or unsubstituted naphthoquinones, N oxides, nitroso compounds, hydroxylamines, oxines, flavins, phenazines, phenazine derivatives, phenothiazines, indophenols, and indamines. These, and other mediators that may be included in the reagent layer may be found in U.S. Pat. Nos. 5,653,863; 5,520,786; 4,746,607; 3,791,988; and in EP Patent Nos. 0354441 and 0330517.

At present, especially preferred mediators for glucose analysis include ferricyanide, ruthenium hexaamine, PIPT, PIPO, or combinations thereof. A review of useful electrochemical mediators for biological redox systems may be found in Analytica Clinica Acta, 140 (1982), pages 1-18.

The reagent layers 275, 285 may be deposited by any convenient means, such as printing, liquid deposition, or ink-jet deposition. In one aspect, the layers are deposited by printing. With other factors being equal, the angle of the printing blade may inversely affect the thickness of the reagent layers. For example, when the blade is moved at an approximately 82° angle to the base 110, the layer may have a thickness of approximately 10 μm. Similarly, when a blade angle of approximately 62° to the base 110 is used, a thicker 30 μm layer may be produced. Thus, lower blade angles may provide thicker reagent layers. In addition to blade angle, other factors, such as the viscosity of the material being applied as well as the screen-size and emulsion combination, may affect the resulting thickness of the reagent layers 275, 285.

The working electrode 175 also may include a diffusion barrier layer (DBL) that is integral to a reagent layer 275 or that is a distinct layer 290, such as depicted in FIG. 2. Thus, the DBL may be formed as a combination reagent/DBL on the conductor, as a distinct layer on the conductor, or as a distinct layer on the reagent layer. When the working electrode 175 includes the distinct DBL 290, the reagent layer 275 may or may not reside on the DBL 290. Instead of residing on the DBL 290, the reagent layer 275 may reside on any portion of the sensor strip 100 that allows the reagent to solubilize in the sample. For example, the reagent layer 175 may reside on the base 110 or on the lid 120.

The DBL provides a porous space having an internal volume where a measurable species may reside. The pores of the DBL may be selected so that the measurable species may diffuse into the DBL, while physically larger sample constituents, such as RB cells, are substantially excluded. Although conventional sensor strips have used various materials to filter RB cells from the surface of the working electrode, a DBL provides an internal porous space to contain and isolate a portion of the measurable species from the sample.

When the reagent layer 275 includes a water-soluble binder, any portion of the binder that does not solubilize into the sample prior to the application of an excitation may function as an integral DBL. The average initial thickness of a combination DBL/reagent layer is preferably less than 30 or 23 micrometers (μm) and more preferably less than 16 μm. At present, an especially preferred average initial thicknesses of a combination DBL/reagent layer is from 1 to 30 μm or from 3 to 12 μm. The desired average initial thickness of a combination DBL/reagent layer may be selected for a specific excitation length on the basis of when the diffusion rate of the measurable species from the DBL to a conductor surface, such as the surface of the conductor 170 or the surface of the surface conductor 270 from FIG. 2, becomes relatively constant.

Furthermore, using too thick of a DBL with a short excitation length may delay when the diffusion rate of the measurable species from the DBL to the conductor surface becomes relatively constant. For example, when duty cycles including sequential 1 second excitations separated by 0.5 second relaxations are applied to a working electrode using a combination DBL/reagent layer having an average initial thickness of 30 μm, a preferred diffusion rate may not be reached until at least 6 duty cycles have been applied (>˜10 seconds). Conversely, when the same duty cycles are applied to a working electrode using a combination DBL/reagent layer having an average initial thickness of 11 μm, a relatively constant diffusion rate may be reached after the second excitation (˜2.5 seconds). Thus, there is an upper limit for the preferred average initial thickness of the DBL for a given duty cycle. A more in-depth treatment of the correlation between DBL thickness, excitation length, and time to reach a relatively constant diffusion rate may be found in U.S. Provisional App. No. 60/655,180, filed Feb. 22, 2005, entitled “Concentration Determination in a Diffusion Barrier Layer”.

The distinct DBL 290 may include any material that provides the desired pore space, while being partially or slowly soluble in the sample. In one aspect, the distinct DBL 290 may include a reagent binder material lacking reagents. The distinct DBL 290 may have an average initial thickness of at least 5 μm, preferably, from 8 to 25 μm, and more preferably from 8 to 15 μm.

FIG. 3 represents an electrochemical analysis 300 for determining the presence and optionally the concentration of an analyte 322 in a sample 312. In 310, the sample 312 is introduced to a sensor strip 314, such as the sensor strip depicted in FIGS. 1A-1B and 2. The reagent layers, such as 275 and/or 285 from FIG. 2, begin to solubilize into the sample 312, thus allowing reaction. At this point in the analysis, it may be beneficial to provide an initial time delay, or “incubation period,” for the reagents to react with the sample 312. Preferably, the initial time delay may be from 1 to 10 seconds. A more in-depth treatment of initial time delays may be found in U.S. Pat. Nos. 5,620,579 and 5,653,863.

During the reaction, a portion of the analyte 322 present in the sample 312 is chemically or biochemically oxidized or reduced in 320, such as by an oxidoreductase. Upon oxidation or reduction, electrons optionally may be transferred between the analyte 322 and a mediator 332 in 330.

In 340, a measurable species 342, which may be the charged analyte 322 from 320 or the charged mediator 332 from 330, is electrochemically excited (oxidized or reduced). For example, when the sample 312 is whole blood containing glucose that was oxidized by glucose oxidase in 320, which then transfers an electron to reduce a ferricyanide (III) mediator to ferrocyanide (II) in 330, the excitation of 340 oxidizes ferrocyanide (II) to ferricyanide (III) at the working electrode. In this manner, an electron is selectively transferred from the glucose analyte to the working electrode of the sensor strip where it may be detected by a measuring device.

The current resulting from the excitation 340 may be recorded during the excitation 340 as a function of time in 350. In 360, the sample undergoes relaxation. Preferably, the current is not recorded during the relaxation 360.

In 370, the excitation 340, the recordation 350, and the relaxation 360 are repeated at least twice for a total of at least three duty cycles within a 180 second or less timeframe. The recorded current and time values may be analyzed to determine the presence and/or concentration of the analyte 322 in the sample 312 in 380.

Amperometric sensor systems apply a potential (voltage) to the sensor strip to excite the measurable species while the current (amperage) is monitored. Conventional amperometric sensor systems may maintain the potential while measuring the current for a continuous read pulse length of from 5 to 10 seconds, for example. In contrast to conventional methods, the duty cycles used in the electrochemical analysis 300 replace continuous, long-duration read pulses with multiple excitations and relaxations of short duration.

The analysis 300 may increase the accuracy and/or precision of the analyte determination when the measurable species excited at the working electrode in 540 is substantially drawn from the interior of a DBL, as opposed to the measurable species present in the cap-gap of the strip. FIGS. 4A and 4B depict a working electrode 400 having a surface conductor 430 and a distinct DBL 405 during the application of a long read pulse and a short excitation. When a WB sample is applied to the working electrode 400, RB cells 420 cover the DBL 405. Analyte present in the sample forms external measurable species 410 external to the DBL 405. A portion of the external measurable species 410 diffuses into the distinct DBL 405 to give internal measurable species 415.

As shown in FIG. 4A, when a continuous 10 second read pulse is applied to the working electrode 400, both the external and internal measurable species 410 and 415 are excited at the surface conductor 430 by a change in oxidation state. During the long read pulse, the external measurable species 410 diffuses through the sample region where the RB cells 420 reside and through the DBL 405 to the surface conductor 430. Diffusion of the external measurable species 410 through the RB cells 420 during the read pulse introduces the hematocrit effect to the analysis. Because a substantial portion of the measurable species excited at the surface conductor 430 originates from outside the DBL 420, a long read pulse applied to a sensor strip having a DBL may perform similarly with regards to the hematocrit effect to a short read pulse applied to a strip lacking a DBL.

Conversely, FIG. 4B represents the situation where a short excitation is applied to the DBL equipped sensor strip 400 to excite the internal measurable species 415, while substantially excluding from excitation the measurable species 410 external to the DBL 405. During the short excitation, the measurable species 410 either remains external to the DBL 405 or does not substantially diffuse through the DBL to reach the surface conductor 430. In this manner, the short excitation may provide a substantial reduction in the influence of the hematocrit effect on the analysis.

By controlling the length of excitation at the working electrode, the measurable species internal to the DBL may be analyzed, while the measurable species external to the DBL may be substantially excluded from analysis. In relation to the surface conductor 430 of the working electrode, the thickness and internal volume of the DBL 405 is believed to alter the diffusion rate of the internal measurable species 415 in relation to the diffusion rate of the external measurable species 410.

Because the measurable species internal to the DBL may diffuse at a different rate to the conductor of the working electrode than the measurable species external to the DBL, the length of the excitation at the working electrode may select which measurable species is preferentially analyzed. While identical from a molecular standpoint, the different diffusion rates of the measurable species internal and external to the DBL may allow differentiation.

While not wishing to be bound by any particular theory, it is presently believed that the rate of diffusion of the measurable species from outside the DBL into the DBL is varying, while the diffusion rate of the measurable species from the internal volume of the DBL to the conductor is relatively constant. The varying rate of diffusion of the measurable species outside the DBL may be caused by the RB cells and other constituents present in the sample and may give rise to the hematocrit effect. Thus, analysis errors (bias) introduced by the sample constituents, including RB cells, may be reduced by substantially limiting analysis to the measurable species having a relatively constant diffusion rate to the conductor.

Another advantage of selectively analyzing the measurable species internal to the DBL is a reduction of measurement imprecision from sensor strips having varying cap-gap volumes. If a read pulse continues past the time when substantially all of the measurable species present in the cap-gap has been analyzed, the analysis no longer represents the concentration of measurable species in the sample, but has instead determined the amount of measurable species in the cap-gap; a very different measurement. As the excitation length becomes long relative to the volume of the cap-gap, the current measurement will depend on the volume of the cap-gap, not the underlying analyte concentration. Thus, long read pulses may result in measurements that are highly inaccurate with regard to analyte concentration when the pulse length “overshoots” the measurable species present in the cap-gap.

As described in U.S. Provisional App. No. 60/617,889, filed Oct. 12, 2004, entitled “Concentration Determination in a Diffusion Barrier Layer,” a single short read pulse or excitation may be selected to substantially limit measurable species excitation to a DBL. When a single excitation is used, the length of the excitation and the thickness of the DBL may be preferably selected so that a relatively constant diffusion rate of the measurable species from the DBL to the conductor surface is reached during the excitation. If a relatively constant diffusion rate is not reached during the excitation, the concentration of the measurable species within the DBL may not accurately represent the concentration of the measurable species in the sample, thus adversely affecting the analysis. Furthermore, the single excitation may not effectively reduce the background signal from the mediator.

Referring to FIG. 3, the excitation 340, the recordation 350, and the relaxation 360 constitute a single duty cycle, which may be applied to a sensor strip at least three times during a 180 second or less time period. More preferably, at least 4, 6, 8, 10, 14, 18, or 22 duty cycles are applied during an independently selected 120, 90, 60, 30, 15, 10, or 5 second time period. In one aspect, the duty cycles are applied during a 5 to 60 second time period. In another aspect, from 3 to 18 or from 3 to 10 duty cycles may be applied within 30 seconds or less. In another aspect, from 4 to 8 duty cycles may be applied within 3 to 16 seconds.

The potential applied during the excitation 340 portion of the duty cycle is preferably applied at a substantially constant voltage and polarity throughout its duration. This directly contrasts to conventional read pulses where the voltage is changed or “swept” through multiple voltage potentials and/or polarities during data recordation. In one aspect, the duration of the excitation 340 is at most 4 or 5 seconds, and preferably less than 3, 2, 1.5, or 1 second. In another aspect, the duration of the excitation 340 is from 0.01 to 3 seconds, from 0.01 to 2 seconds, or from 0.01 to 1.5 seconds. More preferably, the duration of the excitation 340 is from 0.1 to 1.2 seconds.

After the excitation 340, in 360 the measuring device may open the circuit through the sensor strip 314, thus allowing the system to relax. During the relaxation 360, the current present during the excitation 340 is substantially reduced by at least one-half, preferably by an order of magnitude, and more preferably to zero. Preferably, a zero current state is provided by an open circuit or other method known to those of ordinary skill in the art to provide a substantially zero current flow. At least 3 relaxations may be provided during the duty cycles of the pulse sequence.

In one aspect, the relaxation 360 is at least 10, 5, 3, 2, 1.5, 1, or 0.5 seconds in duration. In another aspect, the relaxation 360 is from 0.1 to 3 seconds, from 0.1 to 2 seconds, or from 0.1 to 1.5 seconds in duration. More preferably, the relaxation 360 is from 0.2 to 1.5 seconds in duration and provided by an open circuit.

During the relaxation 360, the ionizing agent may react with the analyte to generate additional measurable species without the effects of an electric potential. Thus, for a glucose sensor system including glucose oxidase and a ferricyanide mediator as reagents, additional ferrocyanide (reduced mediator) responsive to the analyte concentration of the sample may be produced without interference from an electric potential during the relaxation 360.

Many conventional analysis methods continuously apply a voltage during the duration of the read pulse. The applied voltage may have a fixed potential or may have a potential that is swept from a positive to a negative potential or from a positive or a negative potential to a zero potential relative to a potential. Even at a zero relative potential, these methods continuously draw current from the sensor strip during the read pulse, which permits the electrochemical reaction to continue throughout the read pulse. Thus, the reaction that produces measurable species responsive to the analyte concentration and the diffusion of the measurable species to the working electrode are both affected by current during the zero potential portion of a conventional read pulse.

Conventional methods that continuously apply voltage to and draw current from the sensor strip, even at a zero potential in relation to a potential, are fundamentally different from the relaxations of the present invention. The multiple duty cycles applied by the present invention also are markedly different from conventional methods that use a single long duration pulse with multiple measurements, such as those disclosed in U.S. Pat. No. 5,243,516, due to the multiple relaxations of the present invention. In contrast to these conventional methods, each duty cycle of the pulse sequences of the present invention provides an independent diffusion and analyte reaction time during the relaxation.

FIGS. 5A-5E depict five examples of gated amperometric pulse sequences where multiple duty cycles were applied to the sensor strip after introduction of the sample. In these examples, square-wave pulses were used; however, other wave types compatible with the sensor system and the test sample also may be used. FIGS. 5C-5D depict pulse sequences including multiple duty cycles having the same excitation and open circuit delay times.

FIGS. 5A-5B depict pulse sequences that include 9 duty cycles having the same excitation and open circuit delay times in addition to a terminal read pulse 510 of longer duration that increases in voltage. The increased voltage of this terminal read pulse provides the ability to detect a species having a higher oxidation potential. A more complete discussion regarding terminal read pulses may be found in U.S. Provisional App. No. 60/669,729, filed Apr. 8, 2005, entitled “Oxidizable Species as an Internal Reference in Control Solutions for Biosensors.”

FIG. 5A depicts a 9 duty cycle pulse sequence where 0.5 second excitations are separated by 1 second open circuit delays to give a redox intensity (RI) of 0.357 (5/14). Thus, in FIG. 5A, the second duty cycle has an excitation portion 520 and a relaxation portion 530. FIG. 5B depicts a 9 duty cycle pulse sequence where 1 second excitations are separated by 0.5 second open circuit delays to give a RI of 0.69 (10/14.5). FIG. 5C depicts an 7 duty cycle pulse sequence where 1 second excitations are separated by 1 second open circuit delays to give a RI of 0.53 (8/15). A terminal read pulse 540 of the same duration and voltage as those used during the 7 duty cycles was applied. FIG. 5D depicts a 6 duty cycle pulse sequence where 1.5 second excitations are separated by 1 second open circuit delays to give a RI of 0.636 (10.5/16.5). As in FIG. 5C, the terminal read pulse 540 of the same duration and voltage as the prior duty cycle pulses was applied. FIG. 5E depicts a 7 duty cycle pulse sequence where relatively short 0.25 second excitations are separated by relatively long 1.5 second relaxations. The FIG. 5E pulse sequence begins with an initial 1 second pulse 550 and ends with the 1.25 second terminal read pulse 540 to provide a RI of 0.25 (4/16).

The higher the RI for a pulse sequence, the less background will be introduced into the analysis by the mediator. The pulse sequences represented in FIGS. 5A-5E are oxidative pulses, designed to excite (i.e. oxidize) a reduced mediator, which is the measurable species. Thus, the greater the oxidative current applied to the sensor strip in a given time period, the less chance that mediator reduced by pathways other than oxidation of the analyte is contributing to the recorded current values.

Table III, below, provides the slope, intercept, and ratio of intercept-to-slope for the contour profiles of the last four duty cycles of pulse sequences (a) and (b). Pulse sequence (a) was:

9×(0.5 sec on+1.0 sec off)+0.5 sec=14 sec, RI=5/14=0.357.

Pulse sequence (b) was:

9×(1.0 sec on+0.375 sec off)+1.0 sec=13.375 sec, RI=10/13.375=0.748

TABLE III
Pulse Sequence (a), Pulse Sequence (b),
RI = 0.357 RI = 0.748
Pulse # Slope Intercept Int/Slope Slope Intercept Int/Slope
7 20.5 2581.6 125.93 14.07 741.29 52.69
8 19.99 2239.4 112.03 13.47 649.93 48.25
9 19.53 1973.4 101.04 12.92 580.94 44.96
10 19.1 1762.5 92.28 12.45 525.26 42.19

The intercept-to-slope ratios provide an indication of the amount of background signal attributable to the mediator, with higher ratio values indicating a greater proportion of the recorded signal attributable to mediator background. Thus, while the pulse frequency (number of excitations/total assay time in seconds) of sequences (a) and (b) are similar at about 0.7 sec−1, the increase in RI provided by pulse sequence (b) provides less than half as much background signal. In combination, the multiple excitations of the pulse sequence may eliminate the need for an initial pulse to renew the oxidation state of the mediator. While the background current may be influenced by the mediator, for ferricyanide, pulse sequences having RI values of at least 0.01, 0.3, 0.6, or 1 are preferred, with RI values of from 0.1 to 0.8, from 0.2 to 0.7, or from 0.4 to 0.6 being more preferred.

Referring back to FIG. 3, in 350 the current passing through the conductors of the sensor strip 314 for each duty cycle of the pulse sequence may be recorded as a function of time. FIG. 6A shows the output currents plotted as a function of time for the pulse sequence represented in FIG. 5B for 40% hematocrit WB samples containing 50, 100, 200, 400, and 600 mg/dL glucose. Instead of a conventional long duration read pulse resulting in extensive oxidation of the measurable species, each excitation is followed by a break in the current profile.

In FIG. 6A, when the output currents are plotted as a function of time, each excitation results in a transient current profile having an initial high current value that decays over time. Preferably, the duty cycles include short, independent excitations and relaxations that inhibit the system from reaching a steady-state or a slow current decay condition during each excitation, as required during the read pulse of conventional systems. Instead of conventional steady-state or slowly decaying currents, transient (rapidly decaying) current values are obtained from the gated amperometric pulse sequences because the electrochemical reaction of the measurable species at the working electrode is faster than the rate at which the measurable species is supplied to the working electrode by diffusion.

FIG. 6B shows a contour profile plot prepared by connecting the final current value from each of the transient current profiles (i.e. the final current value from each excitation) shown in FIG. 6A. The contour profile may be used to simulate the data obtained from a conventional system at steady-state, where the current change with time is substantially constant.

The transient current profiles obtained from gated amperometric pulse sequences and the derived contour current values are fundamentally different from the current profiles obtained from a conventional analysis using a single read pulse. While currents recorded from a single read pulse derive from a single relaxation/diffusion, each time point in the contour profile of the transient currents originates from an excitation after an independent relaxation/diffusion process. Furthermore, as the length of an excitation increases, the correlation between the current and the analyte concentration may decrease, often due to the hematocrit effect. Thus, the accuracy of an analysis using multiple, short excitations may be increased in comparison to an analysis using a longer read pulse having the duration of the multiple excitations combined.

Referring back to FIG. 6A, a transient point 605 is reached in the current profile when the last in time current value obtained for an excitation represents the greatest last in time current value obtained for any excitation. Thus, for FIG. 6A the transient point is reached at approximately 5 seconds. For each of the glucose concentrations, equilibrium with regards to DBL re-hydration may be reached at the highest current value in the contour profile for each glucose concentration. Thus, when the transient currents of FIG. 6A are converted to contour currents in FIG. 6B, reading 610 (highest) and 620 (lower) establish that equilibrium was reached regarding diffusion of the measurable species into the DBL and re-hydration of the DBL at about five seconds for the 600 mg/dL glucose concentration.

Current values recorded at a relatively constant diffusion rate minimize inaccuracies that would otherwise be introduced by variations in the rehydration and diffusion rates of the reagents. Thus, once a relatively constant diffusion rate is reached, the recorded current values more accurately correspond to the concentration of the measurable species, and thus the analyte. Furthermore, for FIG. 6B, the complete analysis may be completed in as few as seven seconds because once the highest current value 610 of the contour profile is known, its value may be directly correlated to the analyte concentration. Additional data points may be obtained to reduce background error attributable to the mediator, as previously discussed.

FIG. 6C shows current contour profiles prepared from transient current profiles generated by the pulse sequence depicted in FIG. 5E. During each 0.25 second excitation, current values were recorded at the middle (0.125 second) and end (˜0.25 second), which may be used to determine a decay constant. Using the longer initial pulse with the short excitations and relatively long relaxations, the analysis may be completed in about four seconds.

FIG. 6D is a graph illustrating output signals in relation to input signals for an electrochemical system using gated amperometric pulse sequences. The input signals are potentials applied to a sample of biological fluid. The input signals include a polling input signal and an assay input signal. The output signals are currents generated from the sample. The output signals include a polling output signal and an assay output signal. The sample generates the assay output signal from a redox reaction of glucose in whole blood in response to the assay input signal. The input and output signals may be for a biosensor having working and counter electrodes. Other biosensors may be used including those with additional electrodes and different configurations. Other analyte concentrations may be measured including those in other biological fluids. Other output signals may be generated including those that decline initially and those that decline in all pulses.

In use, a sample of the biological fluid is deposited in a biosensor. The biosensor applies a polling signal to the sample from about −1.25 seconds through about 0 seconds. The pulses have a pulse width of about 5-10 ms and a pulse interval of about 125 ms. The biosensor generates a polling output signal in response to the polling input signal. The biosensor measures the polling output signal. The biosensor may have a potentiostat that provides the polling output signal to the input of an analog comparator.

When the polling output signal is equal to or greater than a polling threshold, the biosensor applies the assay input signal to the electrodes from about 0 seconds through about 7 seconds. The polling threshold valve may be about 250 nA. The comparator may compare the polling output signal to the polling threshold value. When the polling output signal exceeds the polling threshold value, the output signal of the comparator may trigger the launch of the assay input signal.

During the assay input signal, the biosensor applies a duty cycle with a first pulse having a potential of about 400 mV for about 1 sec to the working and counter electrodes. The first pulse is followed by a 0.5 sec relaxation, which may be an essentially open circuit or the like. The assay output signal or current within the first pulse is measured and stored in a memory device. The biosensor may apply a second pulse to the working and counter electrodes at about 200 mV for about 1 sec. The assay output signal or current within the second pulse is measured and stored in a memory device. The biosensor continues applying pulses from the assay input signal to the working and counter electrodes until the end of the assay period or for as long as desired by the biosensor. The assay period may be about 7 seconds. The biosensor may measure and store assay output signal or current within each pulse.

The polling input signal is an electrical signal, such as current or potential, that pulses or turns on and off at a set frequency or interval. The sample generates a polling output signal in response to the polling input signal. The polling output signal is an electrical signal, such as current or potential. The biosensor may show the polling output signal on a display and/or may store the assay output signal in a memory device. The biosensor may apply the polling signal to detect when a sample connects with the electrodes. The biosensor may use other methods and devices to detect when a sample is available for analysis.

The polling input signal is duty cycle in which a sequence of polling pulses is separated by polling relaxations. During a polling pulse, the electrical signal is on. During a polling relaxation, the electrical signal is off. On may include time periods when an electrical signal is present. Off may include time periods when an electrical signal is not present. Off may not include time periods when an electrical signal is present but has essentially no amplitude. The electrical signal may switch between on and off by closing and opening an electrical circuit, respectively. The electrical circuit may be opened and closed mechanically, electrically, or the like.

A polling input signal may have one or more polling pulse intervals. A polling pulse interval is the sum of a polling pulse and a polling relaxation. Each polling pulse has an amplitude and a polling pulse width. The amplitude indicates the intensity of the potential, the current, or the like of the electrical signal. The amplitude may vary or be a constant during the polling pulse. The polling pulse width is the time duration of a polling pulse. The polling pulse widths in a polling input signal may vary or be essentially the same. Each polling relaxation has a polling relaxation width, which is the time duration of a polling relaxation. The polling relaxation widths in a polling input signal may vary or be essentially the same.

The polling input signal may have a polling pulse width of less than about 300 milliseconds (ms) and a polling pulse interval of less than about 1 sec. The polling input signal may have a polling pulse width of less than about 100 ms and a polling pulse interval of less than about 500 ms. The polling input signal may have a polling pulse width in the range of about 0.5 ms through about 75 ms and a polling pulse interval in the range of about 5 ms through about 300 ms. The polling input signal may have a polling pulse width in the range of about 1 ms through about 50 ms and a polling pulse interval in the range of about 10 ms through about 250 ms. The polling input signal may have a polling pulse width of about 5 ms and a polling pulse interval of about 125 ms. The polling input signal may have other pulse widths and pulse intervals.

The biosensor may apply the polling input signal to the sample during a polling period. The polling period may be less than about 15 minutes, 5 minutes, 2 minutes, or 1 minute. The polling period may be longer depending upon how a user uses the biosensor. The polling period may be in the range of about 0.5 second (sec) through about 15 minutes. The polling period may be in the range of about 5 sec through about 5 minutes. The polling period may be in the range of about 10 sec through about 2 minutes. The polling period may be in the range of about 20 sec through about 60 sec. The polling period may be in the range of about 30 through about 40 sec. The polling period may have less than about 200, 100, 50, or pulse intervals. The polling period may have from about 2 through about 150 pulse intervals. The polling period may have from about 5 through about 50 pulse intervals. The polling period may have from about 5 through about 15 pulse intervals. The polling period may have about 10 pulse intervals. Other polling periods may be used.

The biosensor applies the assay input signal when the polling output signal is equal to or greater than a polling threshold. The polling threshold may be greater than about 5 percent (%) of the expected assay input signal at the beginning of the first pulse. The polling threshold may be greater than about 15% of the expected assay input signal at the beginning of the first pulse. The polling threshold may be in the range of about 5 percent (%) through about 50% of the expected assay input signal at the beginning of the first pulse. Other polling thresholds may be used. The biosensor may indicate the polling output signal is equal to or greater than the polling threshold on a display.

The assay input signal is an electrical signal, such as current or potential, that pulses or turns on and off at a set frequency or interval. The sample generates an assay output signal in response to the assay input signal. The assay output signal is an electrical signal, such as current or potential.

The assay input signal is a sequence of assay pulses separated by assay relaxations. During an assay pulse, the electrical signal is on. During an assay relaxation, the electrical signal is off. On includes time periods when an electrical signal is present. Off includes time periods when an electrical signal is not present and does not include time periods when an electrical signal is present but has essentially no amplitude. The electrical signal switches between on and off by closing and opening an electrical circuit, respectively. The electrical circuit may be opened and closed mechanically, electrically, or the like.

An assay input signal may have one or more assay pulse intervals. An assay pulse interval is the sum of an assay pulse and an assay relaxation. Each assay pulse has an amplitude and an assay pulse width. The amplitude indicates the intensity of the potential, the current, or the like of the electrical signal. The amplitude may vary or be a constant during the assay pulse. The assay pulse width is the time duration of an assay pulse. The assay pulse widths in an assay input signal may vary or be essentially the same. Each assay relaxation has an assay relaxation width, which is the time duration of an assay relaxation. The assay relaxation widths in an assay input signal may vary or be essentially the same.

The assay input signal may have an assay pulse width of less than about 5 sec and an assay pulse interval of less than about 15 sec. The assay input signal may have an assay pulse width of less than about 3, 2, 1.5, or 1 sec and an assay pulse interval of less than about 13, 7, 4, 3, 2.5, or 1.5 sec. The assay input signal may have an assay pulse width in the range of about 0.1 sec through about 3 sec and an assay pulse interval in the range of about 0.2 sec through about 6 sec. The assay input signal may have an assay pulse width in the range of about 0.1 sec through about 2 sec and an assay pulse interval in the range of about 0.2 sec through about 4 sec. The assay input signal may have an assay pulse width in the range of about 0.1 sec through about 1.5 sec and an assay pulse interval in the range of about 0.2 sec through about 3.5 sec. The assay input signal may have an assay pulse width in the range of about 0.4 sec through about 1.2 sec and an assay pulse interval in the range of about 0.6 sec through about 3.7 sec. The assay input signal may have an assay pulse width in the range of about 0.5 sec through about 1.5 sec and an assay pulse interval in the range of about 0.75 sec through about 2.0 sec. The assay input signal may have an assay pulse width of about 1 sec and an assay pulse interval of about 1.5 sec. The assay input signal may have other pulse widths and pulse intervals.

The biosensor applies the assay input signal to the sample during an assay period. The assay period may have the same or a different duration than the polling period. The assay period of the assay input signal may be less than about 180, 120, 90, 60, 30, 15, 10, or 5 sec. The assay period may be in the range of about 1 sec through about 100 sec. The assay period may be in the range of about 1 sec through about 25 sec. The assay period may be in the range of about 1 sec through about 10 sec. The assay period may be in the range of about 2 sec through about 3 sec. The assay period may be about 2.5 sec. The assay period may have less than about 50, 25, 20, 15, 10, 8, 6, or 4 assay pulse intervals. The assay period may have assay pulse intervals in the range of about 2 through about 50. The assay period may have assay pulse intervals in the range of about 2 through about 25. The assay period may have assay pulse intervals in the range of about 2 through about 15. The assay period may have about 10 assay pulse intervals. Other assay periods may be used.

FIGS. 7A and 7B are graphs illustrating the improvement in measurement accuracy when a DBL is combined with a short read pulse. Whole blood samples were combined with ferrocyanide in a 1:5 dilution ratio to represent an underlying glucose concentration and measured with a 1 second read pulse. Thus, the initial 20%, 40%, and 60% hematocrit WB samples were diluted to 16%, 32%, and 48% hematocrit (a 20% reduction of all three hematocrit values). The 20%, 40%, and 60% lines represent the current measured for the blood samples containing 16%, 32%, and 48% hematocrit, respectively.

FIG. 7A shows the inaccuracies introduced by the hematocrit and other effects from a bare conductor sensor strip lacking a DBL. The inaccuracy is represented as the difference between the 20% and 60% hematocrit lines (the total hematocrit bias span) and represents the maximum measurement inaccuracy attributable to the hematocrit effect. Smaller bias values represent a more accurate result. Similar performance was observed when a DBL was used with a longer read pulse as discussed above with regard to FIG. 4A.

Conversely, FIG. 7B shows a marked decrease in the distance between the 20% and 60% calibration lines when a DBL is combined with a 1 second read pulse. A distinct DBL of PEO polymer and 10% KCl (without reagents) was printed on a conductor as used for FIG. 7A above. The total bias hematocrit span with the DBL/short read pulse was nearly two-thirds less than the total bias span without the DBL. Thus, pulse sequences including multiple duty cycles in combination with a DBL may significantly increase measurement accuracy and provide a desirable reduction in mediator background.

FIGS. 7C and 7D illustrate the reduction in hematocrit bias that may be obtained when a gated amperometric pulse sequence is combined with a DBL. FIG. 7C demonstrates that the measurement bias attributable to hematocrit effect is within ±5% when a DBL was combined with the pulse sequence of FIG. 5E and the current values were recorded at 14.875 seconds or 0.125 seconds from the last pulse. For comparison, FIG. 7D establishes that bias increases to ±15% when current value at 16 seconds (1.25 seconds from the last pulse) is used to determine the glucose concentration of the sample. Thus, the longer the duration of the excitation, the greater the hematocrit bias observed.

In addition to the ability of the present invention to reduce inaccuracy from the hematocrit effect and mediator background signal, the combination of the transient current profile of each excitation and the resulting contour profiles may be used to provide multiple sets of calibration constants to the sensor system, thus increasing the accuracy of the analysis. Each set of calibration constants obtained may be used to correlate a specific current reading to a specific concentration of measurable species in the sample. Thus, in one aspect, an increase in accuracy may be obtained by averaging the glucose values obtained using multiple sets of calibration constants.

Conventional electrochemical sensor systems generally use one set of calibration constants, such as slope and intercept, to convert current readings into corresponding concentration of the analyte in the sample. However, a single set of calibration constants may result in inaccuracies in the analyte concentration determined from the recorded current values because random noise is included in the measurement.

By taking the current value at a fixed time within each duty cycle of the pulse sequences of the present invention, multiple sets of calibration constants may be established. FIG. 8 plots the endpoint currents recorded at 8.5, 10, 11.5, 13, and 14.5 seconds (duty cycles 6-9 and first portion of the terminal read pulse) when the pulse sequence depicted in FIG. 5B was applied to WB samples containing various glucose concentrations. Each of these five calibration lines are independent of the other and may be used in at least two ways.

First, the multiple sets of calibration constants may be used to determine the number of duty cycles that should be applied during the pulse sequence to obtain the desired accuracy, precision, and assay time. For example, if the current values obtained from the first three excitations indicate a high glucose concentration, such as >150 or 200 mg/dL, the sensor system may terminate the analysis at about 5.5 seconds, thus considerably shortening the time required for the analysis. Such a shortening may be possible because imprecision at high glucose concentrations is typically less than at lower glucose concentrations. Conversely, if the current values obtained from the first three excitations indicate a low glucose concentration, such as ≦150 or 100 mg/dL, the sensor system may extend the analysis to greater than 7, such as greater than 8 or 10 seconds, to increase the accuracy and/or precision of the analysis.

Second, the multiple sets of calibration constants may be used to increase the accuracy and/or precision of the analysis by averaging. For example, if the target glucose measurement time is 11.5 seconds, the currents at 8.5, 10, and 11.5 seconds can be utilized to calculate the glucose concentrations using the slopes and intercepts from the corresponding calibration lines; therefore, G8.5=(i8.5−Int8.5)/Slope8.5, G10=(i10−Int10)/Slope10, and G11.5=(i11.5−Int11.5)/Slope11.5. Theoretically, these three glucose values should be equivalent, differing only by random variations. Thus, the glucose values G8.5, G10, and G11.5 may be averaged and the final glucose value of (G8.5+G10+G11.5)/3 may be calculated. Averaging the values from the calibration lines may provide a reduction in noise at the rate of 1/√3).

An unexpected benefit of gated amperometric pulse sequences including relatively short excitations and relatively long relaxations, such as that depicted in FIG. 5E, is the ability to simplify calibration. While the multiple sets of calibration constants that may be obtained from the transient and contour profiles may provide an advantage to the accuracy of the analysis, a pulse sequence such as depicted in FIG. 5E may provide similar accuracy to that obtained using multiple sets of calibration constants from a single set of calibration constants. While not intending to be bound by any particular theory, this result may be attributable to the relatively long relaxation times in comparison to the short relaxations. The long relaxation times may provide a state where the average rate of measurable species conversion during the excitation is balanced by the rate of measurable species diffusion into the DBL. In this manner, the multiple sets of calibration constants may collapse into a single set and the conversion of the recorded data into an analyte concentration may be simplified by carrying out the averaging process on the recorded current data before determining the analyte concentration.

The combination of the transient current profile of each excitation and the resulting contour profiles also may be used to determine if the sensor strip has been under-filled with sample, thus allowing the user to add additional sample to the sensor strip. In addition to working and counter electrodes, conventional sensor systems may determine an under-fill condition through the use of a third electrode or electrode pair; however, the third electrode or electrode pair adds complexity and cost to the sensor system.

Conventional two electrode systems may be able to recognize that an analysis is “bad,” but may not determine if the reason for the failed analysis was caused by under-fill or a defective sensor strip. The ability to determine if under-fill caused the failure of the analysis is beneficial because it may be corrected by adding additional sample to the same sensor strip and repeating the analysis, thus preventing a good strip from being discarded.

FIG. 9A depicts the transient current profiles obtained from the pulse sequence represented in FIG. 5B for 10 analyses, each using a different sensor strip, where 2.0 μL of sample was introduced to the strip. Depending on the filling speed and the cap-gap volume of a specific sensor strip, 2.0 μL of sample may or may not be enough to fill the strip.

In FIG. 9B the transient current profiles of FIG. 9A were converted to contour profiles of decay rate as a function of time. In one aspect, the decay rate may be represented as a K constant determined by either of the following equations:

K 1 = ln ( i 0.125 ) - ln ( i 1.0 ) ln ( t 0.125 ) - ln ( t 1.0 ) K 2 = ln ( i 0.5 ) - ln ( i 1.0 ) ln ( t 0.5 ) - ln ( t 1.0 )
where the 0.125, 0.5, and 1.0 values are in seconds. Thus, using the K constant of a decay process, the current profiles of FIG. 9A may be converted into the decay constant profiles of FIG. 9B.

FIG. 9B establishes that a substantial difference exists between the decay profiles of the under-filled sensors and the normal-filled sensors, especially in the time range of 3 to 7 seconds. Under-fill may be determined from the decay constant profiles by comparing the difference between the actual decay constant and a previously selected value. For example, if −0.1 is selected as the upper limit for a normal-filled sensor with regard to FIG. 9B, any K1 constant having a value lower than −0.1 determined from excitations during the 3 to 5 second time period may be considered normal-filled. Similarly, any sensor having a K1 value higher than −0.1 may be considered under-filled. In this manner, the under-fill may be determined in response to a decay rate obtained from a transient current profile.

Thus, in FIG. 9B the sensor strips represented by series 3 and 8 were sufficiently filled, while the eight sensor strips represented by series 1-2, 4-7, and 9-10 were under-filled. In this manner, the gated amperometric pulse sequences of the present invention allowed for under-fill detection in a two-electrode sensor strip, a function typically requiring a third electrode for conventional sensor systems. Furthermore, the under-fill determination was made in less than ten seconds, providing time for the measuring device to signal the user, such as by sending a signal to a light emitting device or a display, to add more sample to the strip.

Because under-fill may be determined from the transient current profiles, the same current values used to determine the presence and/or concentration of the analyte may be used to determine if an under-fill condition exists. Thus, under-fill may be determined during the multiple duty cycles of the pulse sequence without lengthening the duration of the electrochemical analysis beyond that required for concentration determination.

The combination of the transient current profile of each excitation and the resulting contour profile also may be used to determine if a change in the temperature of the sample may adversely affect the analysis. Conventional sensor systems include a thermister in the measuring device or on the strip to provide the temperature of the device or strip, respectively. While this temperature is an approximation of the sample temperature, typically, the device or strip is at a different temperature than the sample. The temperature difference between the device or strip and the sample may introduce bias into the analysis.

By determining a decay rate, such as with a K constant as previously discussed, the temperature of the sample may be determined. FIG. 10 depicts K constants plotted as a function of temperature that were obtained from the fifth excitation of a pulse sequence for glucose concentrations of 50, 100, and 400 mg/dL. The plots establish that the decay rate increased in absolute value with increasing temperature. While not wishing to be bound by any particular theory, this phenomenon may be attributed to lower temperatures slowing down the diffusion rate of the various constituents present in the cap-gap. In this manner, the temperature of a sample may be determined in response to a decay rate obtained from a transient current profile.

Because sample temperature may be determined from the transient current profiles, the same current values used to determine the presence and/or concentration of the analyte may be used to determine the temperature of the sample. Thus, the temperature of the sample may be determined during the multiple duty cycles of the pulse sequence without lengthening the duration of the electrochemical analysis beyond that required for concentration determination.

In one aspect, the temperature of the sample may be determined by solving for K by the following equation:

K = ln i 0.125 - ln i 0.375 ln ( 0.125 ) - ln ( 0.375 )
where i0.125 and i0.375 are the currents at 0.125 and 0.375 seconds from the excitation most sensitive to temperature change, such as the excitation generating the most sensitive current decay with respect to the temperature change. ln(0.125) and ln(0.375) are the natural logarithmic terms of the times at 0.125 and 0.375 seconds, respectively. From the plot of these K constants verses temperature, as depicted in FIG. 10, the temperature of the sample may be determined by the correlation function of the plot. The correlation function may be a polynomial fit of the curve. The temperature determined from this plot may be different from the temperature of the device and may more accurately reflect the temperature of the sample.

An advantage of determining the temperature of the sample, as opposed to the device, is that the length of the analysis may be adjusted to allow sufficient time for the rehydration of a DBL to reach equilibrium, thus increasing the accuracy of the analysis. For example, if the temperature of the sample determined during the pulse sequence is at least 5 or 10° C. below ambient temperature, the pulse sequence may be lengthened, such as with additional duty cycles.

FIG. 11 is a schematic representation of a measuring device 1100 including contacts 1120 in electrical communication with electrical circuitry 1110 and a display 1130. In one aspect, the measuring device 1100 is portable and is adapted to be handheld and to receive a sensor strip, such as the strip 100 from FIG. 1A. In another aspect, the measuring device 1100 is a handheld measuring device adapted to receive a sensor strip and implement gated amperometric pulse sequences.

The contacts 1120 are adapted to provide electrical communication with the electrical circuitry 1110 and the contacts of a sensor strip, such as the contacts 170 and 180 of the sensor strip 100 depicted in FIG. 1B. The electrical circuitry 1110 may include an electric charger 1150, a processor 1140, and a computer readable storage medium 1145. The electrical charger 1150 may be a potentiostat, signal generator, or the like. Thus, the charger 1150 may apply a voltage to the contacts 1120 while recording the resulting current to function as a charger-recorder.

The processor 1140 may be in electrical communication with the charger 1150, the computer readable storage medium 1145, and the display 1130. If the charger is not adapted to record current, the processor 1140 may be adapted to record the current at the contacts 1120.

The computer readable storage medium 1145 may be any storage medium, such as magnetic, optical, semiconductor memory, and the like. The computer readable storage medium 1145 may be a fixed memory device or a removable memory device, such as a removable memory card. The display 1130 may be analog or digital, in one aspect a LCD display adapted to displaying a numerical reading.

When the contacts of a sensor strip containing a sample are in electrical communication with the contacts 1120, the processor 1140 may direct the charger 1150 to apply a gated amperometric pulse sequence to the sample, thus starting the analysis. The processor 1140 may start the analysis in response to the insertion of a sensor strip, the application of a sample to a previously inserted sensor strip, or in response to a user input, for example.

Instructions regarding implementation of the gated amperometric pulse sequence may be provided by computer readable software code stored in the computer readable storage medium 1145. The code may be object code or any other code describing or controlling the functionality described in this application. The data that results from the gated amperometric pulse sequence may be subjected to one or more data treatments, including the determination of decay rates, K constants, slopes, intercepts, and/or sample temperature in the processor 1140 and the results, such as a corrected analyte concentration, output to the display 1130. As with the instructions regarding the pulse sequence, the data treatment may be implemented by the processor 1140 from computer readable software code stored in the computer readable storage medium 1145.

Without limiting the scope, application, or implementation, the methods and systems previously described may be implemented using the following algorithm:

Step 1: Turn on biosensor power

Step 2: Perform biosensor self-test

Step 3: Setup to poll for application of sample to sensor

    • Set ASIC polling potential to vpoll
    • Set ASIC threshold level to itrigger
    • Set polling periodic timer to expire at intpoll

Step 4: Setup for assaying the sensor current

    • Wait for polling periodic timer to expire
    • Enable ASIC charge pump
    • Enable ASIC threshold detector (itrigger)
    • Enable polling potential (vpoll)
    • Select sensor channel which applies potential to sensor
    • Wait for settling time tpoll

Step 5: Test if the sensor current exceeds the threshold

Step 6: Delay and test sensor current again

Step 7: Upon detection of Sample Application

    • start counting time
    • launch pulse sequence

Step 8: Pulse 1—Measure sensor currents i1,1 and i1,8

    • Pulse 1 starts at time tp1
    • Set Pulse 1 duration to dp1
    • Set Pulse 1 sensor potential to vp1
    • Select sensor channel to apply potential to sensor
    • At time t1,1, measure sensor signal, save value as ADS11
    • At time t1,8, measure sensor signal, save value as ADS18

Step 9: Delay 1—Re-standardize electronics

    • Delay 1 starts at end of AD2 reading, disconnect sensor channel
    • Delay 1 ends at beginning of Pulse 2
    • Set potential to Vstandardize
    • At time tc1, select reference resistor channel then measure signal, save value as ADR1
    • At time tc2, select offset channel then measure signal, save value as ADO1
    • Note: sensor currents starting at Pulse 1 are calculated from the ADR1 and ADO1 measurements

Step 10: Pulse 2—Measure sensor currents i2,1 and i2,8

    • Pulse 2 starts at time tp2
    • Set Pulse 2 duration to dp2
    • Set Pulse 2 sensor potential to Vp2
    • Select sensor channel to apply potential to sensor
    • At time t2,1, measure sensor signal, save value as ADS21
    • At time t2,8, measure sensor signal, save value as ADS28

Step 11: Delay 2—

    • Delay 2 starts at end of ADS3 reading, disconnect sensor channel
    • Delay 2 ends at beginning of Pulse 3
    • Select offset channel to disconnect sensor

Step 12: Pulse 3—Measure sensor currents: i3,1 and i3,8

    • Pulse 3 starts at time tp3
    • Set Pulse 3 duration to dp3
    • Set Pulse 3 sensor potential to vp3
    • Select sensor channel to apply potential to sensor
    • At time t3,1, measure sensor signal, save value as ADS31
    • At time t3,8, measure sensor signal, save value as ADS38

Step 13: Delay 3—T1 and iwet

    • Delay 3 starts at end of ADS38 reading, disconnect sensor channel
    • Delay 3 ends at beginning of Pulse 4
    • Set potential to Vstandardize
    • At time tc3, select thermistor channel then measure signal, save value as ADT1
    • At time twet, select offset channel then measure signal, save value as ADwet

Step 14: Pulse 4—Measure sensor currents: i4,1, i4,4, and i4,8

    • Pulse 4 starts at time tp4
    • Set Pulse 4 duration to dp4
    • Set Pulse 4 sensor potential to vp4
    • Select sensor channel to apply potential to sensor
    • At time t4,1, measure sensor signal, save value as ADS41
    • At time t4,4, measure sensor signal, save value as ADS44
    • At time t4,8, measure sensor signal, save value as ADS48

Step 15: Delay 4—

    • Delay 4 starts at end of ADS48 reading, disconnect sensor channel
    • Delay 4 ends at beginning of Pulse 5
    • Select offset channel to disconnect sensor

Step 16: Pulse 5—Measure sensor currents: i5,1, i5,4, and i5,8

    • Pulse 5 starts at time tp5
    • Set Pulse 5 duration to dp5
    • Set Pulse 5 sensor potential to vp5
    • Select sensor channel to apply potential to sensor
    • At time t5,1, measure sensor signal, save value as ADS51
    • At time t5,4 measure sensor signal, save value as ADS54
    • At time t5,8, measure sensor signal, save value as ADS58
    • Disable ASIC analog functions

Step 17: Look up slope and intercept for lot calibration number

    • S=Slope value for current lot calibration number
    • Int=Intercept value for current lot calibration number

Step 18: Adjust slope and intercept for temperature effect

Step 19: Calculate glucose concentration at 25° C.

Step 20: Convert to target reference (plasma vs. WB reference)

Step 21: Check underfill

Step 22: Check for “Abnormal Behavior”

Step 23: If low glucose, check again for “Abnormal Behavior”

Step 25: Check for extreme glucose levels

Step 26: Display result

The algorithm may have other subroutines including those to check for errors such as sample temperature and underfill conditions. The constants that may be used in the algorithm are given in Table III below. Other constants may be used.

TABLE III
Constant Description Value Units
Vpoll polling voltage 400 mV
intpoll polling interval 125 ms
tpoll polling duration 10 minutes
itrigger threshold detect trigger current 250 nA
tp1 pulse 1 start time 0 sec
dp1 pulse 1 duration 1 second
vp1 pulse 1 voltage level 400 mV
t1, 1 time of sensor current reading 1 0.125 sec
t1, 8 time of sensor current reading 2 1.00 sec
tc1 Offset reading time 1.125 sec
tc2 Reference reading time 1.25 sec
tp2 pulse 2 start time 1.5 sec
dp2 pulse 2 duration 1 second
vp2 pulse 2 voltage level 200 mV
t2, 1 time of sensor current reading 3 1.625 sec
t2, 8 time of sensor current reading 4 2.50 sec
tp3 pulse 3 start time 3 sec
dp3 pulse 3 duration 1 second
vp3 pulse 3 voltage level 200 mV
t3, 1 time of sensor current reading 5 3.125 sec
t3, 8 time of sensor current reading 6 4.00 sec
tc3 Thermistor reading time 4.125 sec
twet Time of wet sensor current reading 4.25 sec
tp4 pulse 4 start time 4.5 second
dp4 pulse 4 duration 1 second
vp4 pulse 4 voltage level 200 mV
t4, 1 time of sensor current reading 7 4.625 sec
t4, 4 time of sensor current reading 8 5.00 sec
t4, 8 time of sensor current reading 9 5.50 sec
tp5 pulse 5 start time 6 sec
dp5 pulse 5 duration 1 second
vp5 pulse 5 voltage level 200 mV
t5, 1 time of sensor current reading 10 6.125 sec
t5, 4 time of sensor current reading 11 6.50 sec
t5, 8 time of sensor current reading 12 7.00 sec

While various embodiments of the invention have been described, it will be apparent to those of ordinary skill in the art that other embodiments and implementations are possible within the scope of the invention.

Citations de brevets
Brevet cité Date de dépôt Date de publication Déposant Titre
US342020523 mars 19667 janv. 1969Miles LabIndicating device
US350513619 sept. 19667 avr. 1970Union Special Machine CoMethod and apparatus for bonding thermoplastic sheet materials
US35102685 juin 19685 mai 1970Hooker Chemical CorpPreparation of flaked phosphorous acid
US355129529 nov. 196729 déc. 1970Northrop CorpMicrobiological detection and identification system
US35731394 août 196930 mars 1971Masao IdeMethod and apparatus for welding plastic members
US362138116 oct. 196816 nov. 1971Leeds & Northrup CoCoulometric system having compensation for temperature induced viscosity changes
US369083612 nov. 197012 sept. 1972PromoveoDevice for use in the study of chemical and biological reactions and method of making same
US37151927 août 19706 févr. 1973Merck Patent GmbhIndicator strip
US37200933 déc. 197013 mars 1973Us NavyCarbon dioxide indicating meter
US376342221 oct. 19712 oct. 1973Corning Glass WorksMethod and apparatus for electrochemical analysis of small samples of blood
US377060715 oct. 19716 nov. 1973SecretaryGlucose determination apparatus
US377683210 nov. 19704 déc. 1973Energetics ScienceElectrochemical detection cell
US379193325 févr. 197112 févr. 1974GeometRapid methods for assay of enzyme substrates and metabolites
US383803331 août 197224 sept. 1974Hoffmann La RocheEnzyme electrode
US390297030 juil. 19732 sept. 1975Leeds & Northrup CoFlow-through amperometric measuring system and method
US391745316 août 19744 nov. 1975Polaroid CorpMethod and device for determining the concentration of a substance in a fluid
US391962731 mai 197311 nov. 1975Allen Gerald FConductivity measuring method and apparatus utilizing coaxial electrode cells
US392518328 janv. 19749 déc. 1975Energetics ScienceGas detecting and quantitative measuring device
US393761517 déc. 197410 févr. 1976Leeds & Northrup CompanyAuto-ranging glucose measuring system
US394874511 juin 19736 avr. 1976The United States Of America As Represented By The Department Of Health, Education And WelfareEnzyme electrode
US398043718 déc. 197514 sept. 1976Kabushiki Kaisha Kyoto Daiichi KagakuTest strips and methods and apparatus for using the same
US40050021 août 197425 janv. 1977Hoffmann-La Roche Inc.Apparatus for measuring substrate concentrations
US40084483 oct. 197515 févr. 1977Polaroid CorporationSolenoid with selectively arrestible plunger movement
US404090812 mars 19769 août 1977Children's Hospital Medical CenterPolarographic analysis of cholesterol and other macromolecular substances
US405338119 mai 197611 oct. 1977Eastman Kodak CompanyDevice for determining ionic activity of components of liquid drops
US406526314 juin 197627 déc. 1977Woodbridge Iii Richard GAnalytical test strip apparatus
US40778615 nov. 19767 mars 1978Teledyne Industries, Inc.Polarographic sensor
US41237011 juil. 197631 oct. 1978United States Surgical CorporationDisposable sample card having a well with electrodes for testing a liquid sample
US412744828 févr. 197728 nov. 1978Schick Karl GAmperometric-non-enzymatic method of determining sugars and other polyhydroxy compounds
US413749525 mars 197730 janv. 1979Brown David M BOil detector
US418493624 juil. 197822 janv. 1980Eastman Kodak CompanyDevice for determining ionic activity
US42149685 avr. 197829 juil. 1980Eastman Kodak CompanyIon-selective electrode
US421719629 mai 197912 août 1980Albert HuchDish-electrode concentration meter with detachable transducer
US422412526 sept. 197823 sept. 1980Matsushita Electric Industrial Co., Ltd.Enzyme electrode
US42254104 déc. 197830 sept. 1980Technicon Instruments CorporationIntegrated array of electrochemical sensors
US422942622 févr. 197821 oct. 1980Duke University, Inc.Breast cyst fluid protein assay
US423053718 déc. 197528 oct. 1980Monsanto CompanyDiscrete biochemical electrode system
US423302925 oct. 197811 nov. 1980Eastman Kodak CompanyLiquid transport device and method
US42606806 oct. 19787 avr. 1981Mitsubishi Chemical Industries, Ltd.Method and apparatus for the measurement of glucose content
US426334313 août 197921 avr. 1981Eastman Kodak CompanyReference elements for ion-selective membrane electrodes
US426525023 juil. 19795 mai 1981Battle Research And Development AssociatesElectrode
US427363920 juin 197916 juin 1981Eastman Kodak CompanyCapillary bridge in apparatus for determining ionic activity
US429718419 févr. 198027 oct. 1981United Chemi-Con, Inc.Method of etching aluminum
US429756928 juin 197927 oct. 1981Datakey, Inc.Microelectronic memory key with receptacle and systems therefor
US430141229 oct. 197917 nov. 1981United States Surgical CorporationLiquid conductivity measuring system and sample cards therefor
US430388729 oct. 19791 déc. 1981United States Surgical CorporationElectrical liquid conductivity measuring system
US43235366 févr. 19806 avr. 1982Eastman Kodak CompanyMulti-analyte test device
US43296429 mars 197911 mai 1982Siliconix, IncorporatedCarrier and test socket for leadless integrated circuit
US436603311 avr. 197928 déc. 1982Siemens AktiengesellschaftMethod for determining the concentration of sugar using an electrocatalytic sugar sensor
US437668913 nov. 198115 mars 1983Matsushita Electric Industrial Co., Ltd.Coenzyme immobilized electrode
US438177518 août 19803 mai 1983Takeda Chemical Industries, Ltd.Method for low pressure filtration of plasma from blood
US439646422 avr. 19822 août 1983Joslin Diabetes Center, Inc.Method for sensing the concentration of glucose in biological fluids
US440294017 sept. 19826 sept. 1983Kuraray Co., Ltd.Method for treating blood plasma employing a hollow fiber membrane
US440398422 déc. 198013 sept. 1983Biotek, Inc.System for demand-based adminstration of insulin
US44072901 avr. 19814 oct. 1983Biox Technology, Inc.Blood constituent measuring device and method
US440795921 oct. 19814 oct. 1983Fuji Electric Co., Ltd.Blood sugar analyzing apparatus
US44134079 nov. 19818 nov. 1983Eastman Kodak CompanyMethod for forming an electrode-containing device with capillary transport between electrodes
US44205644 nov. 198113 déc. 1983Fuji Electric Company, Ltd.Blood sugar analyzer having fixed enzyme membrane sensor
US443100427 oct. 198114 févr. 1984Bessman Samuel PImplantable glucose sensor
US443609427 janv. 198213 mars 1984Evreka, Inc.Monitor for continuous in vivo measurement of glucose concentration
US444017510 août 19813 avr. 1984University Patents, Inc.Membrane electrode for non-ionic species
US447345729 mars 198225 sept. 1984Eastman Kodak CompanyLiquid transport device providing diversion of capillary flow into a non-vented second zone
US44761499 août 19829 oct. 1984Boehringer Mannheim GmbhProcess for the production of an analysis test strip
US447731420 juil. 198316 oct. 1984Siemens AktiengesellschaftMethod for determining sugar concentration
US44775754 août 198116 oct. 1984Boehringer Mannheim GmbhProcess and composition for separating plasma or serum from whole blood
US449021612 janv. 198425 déc. 1984Molecular Devices CorporationLipid membrane electroanalytical elements and method of analysis therewith
US44994238 déc. 198112 févr. 1985Dragerwerk AktiengesellschaftCircuit arrangement for correction of a sensor output
US45029388 avr. 19825 mars 1985Corning Glass WorksEncapsulated chemoresponsive microelectronic device arrays
US451729115 août 198314 mai 1985E. I. Du Pont De Nemours And CompanyBiological detection process using polymer-coated electrodes
US454538222 oct. 19828 oct. 1985Genetics International, Inc.Sensor for components of a liquid mixture
US454773524 janv. 198315 oct. 1985Holger KiesewetterInstrument for measuring the hematocrit value of blood
US455245811 oct. 198312 nov. 1985Eastman Kodak CompanyCompact reflectometer
US456194411 juin 198431 déc. 1985Fuji Photo Film Co., Ltd.Method for producing supports for lithographic printing plates
US457129212 août 198218 févr. 1986Case Western Reserve UniversityApparatus for electrochemical measurements
US457871616 juil. 198425 mars 1986Boehringer Mannheim GmbhMethod of and apparatus for making a test strip and a test strip made by such method
US45798936 janv. 19841 avr. 1986Eastman Kodak CompanyBenzoxazole stabilizer compounds and polymeric materials stabilized therewith
US458268412 sept. 198315 avr. 1986Boehringer Mannheim GmbhCuvette for the photo determination of chemical components in fluids
US45915505 avr. 198427 mai 1986Molecular Devices CorporationDevice having photoresponsive electrode for determining analytes including ligands and antibodies
US462819330 janv. 19809 déc. 1986Blum Alvin SCode reading operations supervisor
US464229515 déc. 198210 févr. 1987Baker John RMethods of determining fructosamine levels in blood samples
US464866515 oct. 198510 mars 1987Amp IncorporatedElectronic key assemblies
US465283018 avr. 198524 mars 1987Eg&G Ocean Products, Inc.Analyzer for comparative measurements of bulk conductivity
US465419712 oct. 198431 mars 1987Aktiebolaget LeoCuvette for sampling and analysis
US467128813 juin 19859 juin 1987The Regents Of The University Of CaliforniaElectrochemical cell sensor for continuous short-term use in tissues and blood
US467665327 août 198430 juin 1987Boehringer Mannheim GmbhApparatus for determining the diffuse reflectivity of a sample surface of small dimensions
US46795629 mai 198614 juil. 1987Cardiac Pacemakers, Inc.Glucose sensor
US468026818 sept. 198514 juil. 1987Children's Hospital Medical CenterImplantable gas-containing biosensor and method for measuring an analyte such as glucose
US468260224 juin 198528 juil. 1987Ottosensor CorporationProbe for medical application
US468647922 juil. 198511 août 1987Young Chung CApparatus and control kit for analyzing blood sample values including hematocrit
US470301714 févr. 198427 oct. 1987Becton Dickinson And CompanySolid phase assay with visual readout
US47037566 mai 19863 nov. 1987The Regents Of The University Of CaliforniaComplete glucose monitoring system with an implantable, telemetered sensor module
US471334714 janv. 198515 déc. 1987Sensor Diagnostics, Inc.Measurement of ligand/anti-ligand interactions using bulk conductance
US471487412 nov. 198522 déc. 1987Miles Inc.Test strip identification and instrument calibration
US47216777 mai 198726 janv. 1988Children's Hospital Medical CenterImplantable gas-containing biosensor and method for measuring an analyte such as glucose
US473172619 mai 198615 mars 1988Healthware CorporationPatient-operated glucose monitor and diabetes management system
US473418426 févr. 198729 mars 1988Diamond Sensor Systems, Inc.Self-activating hydratable solid-state electrode apparatus
US47450769 sept. 198517 mai 1988Hoffmann-La Roche Inc.Ruthenium complexes useful as carriers for immunologically active materials
US47466077 févr. 198524 mai 1988Eastman Kodak CompanyUse of substituted quinone electron transfer agents in analytical determinations
US475049628 janv. 198714 juin 1988Xienta, Inc.Method and apparatus for measuring blood glucose concentration
US47598289 avr. 198726 juil. 1988Nova Biomedical CorporationGlucose electrode and method of determining glucose
US478980417 sept. 19866 déc. 1988Seiko Instruments & Electronics Ltd.Analytical device and method utilizing a piezoelectric crystal biosensor
US479554224 avr. 19863 janv. 1989St. Jude Medical, Inc.Electrochemical concentration detector device
US47972565 juin 198710 janv. 1989Boehringer Mannheim CorporationRegistration device for blood test strips
US480562414 avr. 198721 févr. 1989The Montefiore Hospital Association Of Western PaLow-potential electrochemical redox sensors
US480631128 août 198521 févr. 1989Miles Inc.Multizone analytical element having labeled reagent concentration zone
US480631228 août 198521 févr. 1989Miles Inc.Multizone analytical element having detectable signal concentrating zone
US481020321 déc. 19877 mars 1989Hosiden Electronics Co., Ltd.Electrical connector
US481622431 juil. 198728 mars 1989Boehringer Mannheim GmbhDevice for separating plasma or serum from whole blood and analyzing the same
US482039928 août 198511 avr. 1989Shimadzu CorporationEnzyme electrodes
US482063621 févr. 198611 avr. 1989Medisense, Inc.Electrochemical assay for cis-diols
US483095910 nov. 198616 mai 1989Medisense, Inc.Electrochemical enzymic assay procedures
US483281428 déc. 198723 mai 1989E. I. Du Pont De Nemours And CompanyElectrofusion cell and method of making the same
US48342342 mai 198830 mai 1989Boehringer Mannheim GmbhContainer for test strips
US48493303 mai 198518 juil. 1989Molecular Devices CorporationPhotoresponsive redox detection and discrimination
US48541532 déc. 19878 août 1989Sumitomo Electric Industries, Ltd.Automatic calibration apparatus for a partial gas pressure measuring sensor
US48658737 déc. 198712 sept. 1989General Electric CompanyElectroless deposition employing laser-patterned masking layer
US48775809 févr. 198831 oct. 1989Technimed CorporationAssay kit including an analyte test strip and a color comparator
US489413714 sept. 198716 janv. 1990Omron Tateisi Electronics Co.Enzyme electrode
US48971622 févr. 198830 janv. 1990The Cleveland Clinic FoundationPulse voltammetry
US491977019 déc. 198624 avr. 1990Siemens AktiengesellschaftMethod for determining the concentration of electro-chemically convertible substances
US492751624 juin 198722 mai 1990Terumo Kabushiki KaishaEnzyme sensor
US492933016 oct. 198929 mai 1990Daikin Industries, Ltd.Diffusion-limiting membrane holding means for sensor
US492954514 avr. 198929 mai 1990Boehringer Mannheim CorporationMethod and reagent for determination of an analyte via enzymatic means using a ferricyanide/ferric compound system
US493510518 oct. 198919 juin 1990Imperial Chemical Industries PlcMethods of operating enzyme electrode sensors
US493610629 août 198926 juin 1990White Consolidated Industries, Inc.Retractable control unit for refrigerators
US493634621 déc. 198926 juin 1990Deere & CompanyDetent mechanism for a control valve
US493886028 juin 19853 juil. 1990Miles Inc.Electrode for electrochemical sensors
US49409452 nov. 198710 juil. 1990Biologix Inc.Interface circuit for use in a portable blood chemistry measuring apparatus
US49540872 mars 19904 sept. 1990I-Stat CorporationStatic-free interrogating connector for electric components
US495627514 avr. 198711 sept. 1990Molecular Devices CorporationMigratory detection immunoassay
US496381415 déc. 198916 oct. 1990Boehringer Mannheim CorporationRegulated bifurcated power supply
US497014520 janv. 198813 nov. 1990Cambridge Life Sciences PlcImmobilized enzyme electrodes
US49756471 nov. 19884 déc. 1990Nova Biomedical CorporationControlling machine operation with respect to consumable accessory units
US497672425 août 198911 déc. 1990Lifescan, Inc.Lancet ejector mechanism
US49941677 juil. 198819 févr. 1991Markwell Medical Institute, Inc.Biological fluid measuring device
US499958215 déc. 198912 mars 1991Boehringer Mannheim Corp.Biosensor electrode excitation circuit
US499963215 déc. 198912 mars 1991Boehringer Mannheim CorporationAnalog to digital conversion with noise reduction
US501816412 sept. 198921 mai 1991Hughes Aircraft CompanyExcimer laser ablation method and apparatus for microcircuit fabrication
US501997422 févr. 199028 mai 1991Diva Medical Systems BvDiabetes management system and apparatus
US50358629 déc. 198830 juil. 1991Boehringer Mannheim GmbhAnalytical system for the determination of a component of a fluid
US50396182 févr. 199013 août 1991Hybrivet Systems, Inc.Test swab cartridge type device and method for detecting lead and cadmium
US504661819 nov. 199010 sept. 1991R. P. Scherer CorporationChild-resistant blister pack
US504948711 févr. 198817 sept. 1991Lifescan, Inc.Automated initiation of timing of reflectance readings
US50574479 juil. 199015 oct. 1991Texas Instruments IncorporatedSilicide/metal floating gate process
US50591994 avr. 199022 oct. 1991Olympus Optical Co., Ltd.Treating device for endoscopes
US505939411 févr. 198822 oct. 1991Lifescan, Inc.Analytical device for the automated determination of analytes in fluids
US506637221 juin 199019 nov. 1991Ciba Corning Diagnostics Corp.Unitary multiple electrode sensor
US50750772 août 198824 déc. 1991Abbott LaboratoriesTest card for performing assays
US509666915 sept. 198817 mars 1992I-Stat CorporationDisposable sensing device for real time fluid analysis
US510856415 août 199128 avr. 1992Tall Oak VenturesMethod and apparatus for amperometric diagnostic analysis
US510881914 févr. 199028 avr. 1992Eli Lilly And CompanyThin film electrical component
US511245520 juil. 199012 mai 1992I Stat CorporationMethod for analytically utilizing microfabricated sensors during wet-up
US51127589 mai 198812 mai 1992Epitope, Inc.Treating body fluids for diagnostic testing
US511818313 févr. 19902 juin 1992X-Rite, IncorporatedAutomated strip reader densitometer
US512042031 mars 19899 juin 1992Matsushita Electric Industrial Co., Ltd.Biosensor and a process for preparation thereof
US512042131 août 19909 juin 1992The United States Of America As Represented By The United States Department Of EnergyElectrochemical sensor/detector system and method
US51222444 févr. 199116 juin 1992Boehringer Mannheim GmbhMethod and sensor electrode system for the electrochemical determination of an analyte or an oxidoreductase as well as the use of suitable compounds therefor
US512801513 mars 19897 juil. 1992Tall Oak VenturesMethod and apparatus for amperometric diagnostic analysis
US513199916 janv. 199021 juil. 1992The National University Of SingaporeVoltammetric detector for flow analysis
US51401767 mars 199118 août 1992Advantest CorporationSequential logic circuit device
US51418507 févr. 199025 août 1992Hygeia Sciences, Inc.Porous strip form assay device method
US514186827 nov. 198925 août 1992Internationale Octrooi Maatschappij "Octropa" BvDevice for use in chemical test procedures
US51436944 déc. 19901 sept. 1992Boehringer Mannheim GmbhTest strip evaluating instrument for multiple test strips
US517900528 avr. 198812 janv. 1993Lifescan, Inc.Minimum procedure system for the determination of analytes
US517928830 sept. 199112 janv. 1993Ortho Pharmaceutical CorporationApparatus and method for measuring a bodily constituent
US518270723 juil. 199026 janv. 1993Healthdyne, Inc.Apparatus for recording reagent test strip data by comparison to color lights on a reference panel
US518710019 nov. 199116 févr. 1993Lifescan, Inc.Dispersion to limit penetration of aqueous solutions into a membrane
US51924152 mars 19929 mars 1993Matsushita Electric Industrial Co., Ltd.Biosensor utilizing enzyme and a method for producing the same
US520226118 nov. 199113 avr. 1993Miles Inc.Conductive sensors and their use in diagnostic assays
US521759415 janv. 19928 juin 1993Enzyme Technology Research Group, Inc.Convenient determination of trace lead in whole blood and other fluids
US52209208 nov. 199122 juin 1993Via Medical CorporationElectrochemical measurement system having interference reduction circuit
US52231173 mai 199129 juin 1993Mass. Institute Of TechnologyTwo-terminal voltammetric microsensors
US522928226 nov. 199020 juil. 1993Matsushita Electric Industrial Co., Ltd.Preparation of biosensor having a layer containing an enzyme, electron acceptor and hydrophilic polymer on an electrode system
US52325164 juin 19913 août 1993Implemed, Inc.Thermoelectric device with recuperative heat exchangers
US523266721 mai 19923 août 1993Diametrics Medical, Inc.Temperature control for portable diagnostic system using a non-contact temperature probe
US523266827 févr. 19913 août 1993Boehringer Mannheim CorporationTest strip holding and reading mechanism for a meter
US523481326 août 199110 août 1993Actimed Laboratories, Inc.Method and device for metering of fluid samples and detection of analytes therein
US524351615 déc. 19897 sept. 1993Boehringer Mannheim CorporationBiosensing instrument and method
US524685827 févr. 199121 sept. 1993Boehringer Mannheim CorporationApparatus and method for analyzing a body fluid
US525043914 déc. 19925 oct. 1993Miles Inc.Use of conductive sensors in diagnostic assays
US526141127 déc. 199116 nov. 1993Abbott LaboratoriesThermal drift correction while continuously monitoring cardiac output
US52620352 août 198916 nov. 1993E. Heller And CompanyEnzyme electrodes
US526410315 oct. 199223 nov. 1993Matsushita Electric Industrial Co., Ltd.Biosensor and a method for measuring a concentration of a substrate in a sample
US526617919 juil. 199130 nov. 1993Matsushita Electric Industrial Co., Ltd.Quantitative analysis method and its system using a disposable sensor
US526989126 janv. 199314 déc. 1993Novo Nordisk A/SMethod and apparatus for determination of a constituent in a fluid
US527929426 mars 199018 janv. 1994Cascade Medical, Inc.Medical diagnostic system
US528139518 déc. 199125 janv. 1994Boehringer Manheim GmbhTest carrier analysis system
US528295014 juil. 19921 févr. 1994Boehringer Mannheim GmbhElectrochemical analysis system
US528477024 mai 19938 févr. 1994Boehringer Mannheim CorporationMeter verification method and apparatus
US528636227 avr. 199315 févr. 1994Boehringer Mannheim GmbhMethod and sensor electrode system for the electrochemical determination of an analyte or an oxidoreductase as well as the use of suitable compounds therefor
US528838710 juin 199122 févr. 1994Daikin Industries, Ltd.Apparatus for maintaining the activity of an enzyme electrode
US528863614 déc. 199022 févr. 1994Boehringer Mannheim CorporationEnzyme electrode system
US530446826 janv. 199319 avr. 1994Lifescan, Inc.Reagent test strip and apparatus for determination of blood glucose
US530662326 juil. 199126 avr. 1994Lifescan, Inc.Visual blood glucose concentration test strip
US531142627 oct. 199210 mai 1994Abbott LaboratoriesApparatus and method for providing assay calibration data
US531259024 avr. 198917 mai 1994National University Of SingaporeAmperometric sensor for single and multicomponent analysis
US531276213 sept. 199117 mai 1994Guiseppi Elie AnthonyMethod of measuring an analyte by measuring electrical resistance of a polymer film reacting with the analyte
US532073211 juin 199314 juin 1994Matsushita Electric Industrial Co., Ltd.Biosensor and measuring apparatus using the same
US533247915 mai 199226 juil. 1994Kyoto Daiichi Kagaku Co., Ltd.Biosensor and method of quantitative analysis using the same
US533429628 juin 19932 août 1994Andcare, Inc.Peroxidase colloidal gold oxidase biosensors for mediatorless glucose determination
US534475413 janv. 19936 sept. 1994Avocet Medical, Inc.Assay timed by electrical resistance change and test strip
US53523518 juin 19934 oct. 1994Boehringer Mannheim CorporationBiosensing meter with fail/safe procedures to prevent erroneous indications
US53533519 juin 19924 oct. 1994At&T Bell LaboratoriesSecure teleconferencing
US535444711 déc. 199211 oct. 1994Kyoto Daiichi Kagaku Co., Ltd.Biosensor and method of quantitative analysis using the same
US53666098 juin 199322 nov. 1994Boehringer Mannheim CorporationBiosensing meter with pluggable memory key
US53687077 juin 199329 nov. 1994Andcare, Inc.Convenient determination of trace lead in whole blood and other fluids
US537168720 nov. 19926 déc. 1994Boehringer Mannheim CorporationGlucose test data acquisition and management system
US537625414 mai 199327 déc. 1994Fisher; Arkady V.Potentiometric electrochemical device for qualitative and quantitative analysis
US537921421 oct. 19933 janv. 1995Boehringer Mannheim CorporationMethod for reading the concentration of a medically significant component of a biological fluid from a test strip
US538402827 août 199324 janv. 1995Nec CorporationBiosensor with a data memory
US53858463 juin 199331 janv. 1995Boehringer Mannheim CorporationBiosensor and method for hematocrit determination
US538921527 avr. 199314 févr. 1995Nippon Telegraph And Telephone CorporationElectrochemical detection method and apparatus therefor
US53912728 mars 199421 févr. 1995Andcare, Inc.Electrochemical immunoassay methods
US539390319 févr. 199228 févr. 1995Asulab S.A.Mono, bis or tris(substituted 2,2'-bipyridine) iron, ruthenium, osmium or vanadium complexes and their methods of preparation
US53955041 févr. 19947 mars 1995Asulab S.A.Electrochemical measuring system with multizone sensors
US540346224 juin 19934 avr. 1995Yissum Research Development Company Of The Hebrew Univeristy Of JerusalemElectrochemical electrodes and methods for the preparation thereof
US54055118 juin 199311 avr. 1995Boehringer Mannheim CorporationBiosensing meter with ambient temperature estimation method and system
US541005914 déc. 199325 avr. 1995Asulab S.A.Transition metal complexes having 2,2'-bipyridine ligands substituted by at least one ammonium alkyl radical
US541047427 juil. 199325 avr. 1995Miles Inc.Buttonless memory system for an electronic measurement device
US541164725 janv. 19942 mai 1995Eli Lilly And CompanyTechniques to improve the performance of electrochemical sensors
US541369023 juil. 19939 mai 1995Boehringer Mannheim CorporationPotentiometric biosensor and the method of its use
US54137643 avr. 19909 mai 1995Boehringer Mannheim GmbhTest carrier analysis system
US541814213 oct. 199223 mai 1995Lifescan, Inc.Glucose test strip for whole blood
US542118921 janv. 19946 juin 1995Ciba Corning Diagnostics Corp.Electrical connection system for electrochemical sensors
US542403529 mars 199413 juin 1995Boehringer Mannheim GmbhTest strip analysis system
US54260325 nov. 199320 juin 1995Lifescan, Inc.No-wipe whole blood glucose test strip
US542791227 août 199327 juin 1995Boehringer Mannheim CorporationElectrochemical enzymatic complementation immunoassay
US542973527 juin 19944 juil. 1995Miles Inc.Method of making and amperometric electrodes
US54377721 nov. 19931 août 1995The Electrosynthesis Co., Inc.Portable lead detector
US543799922 févr. 19941 août 1995Boehringer Mannheim CorporationElectrochemical sensor
US543827122 nov. 19941 août 1995Boehringer Mannheim CorporationBiosensing meter which detects proper electrode engagement and distinguishes sample and check strips
US54398262 déc. 19888 août 1995Bio-Tek Instruments, Inc.Method of distinguishing among strips for different assays in an automated instrument
US54459677 oct. 199429 août 1995Boehringer Mannheim GmbhMethod for analyzing a component of a liquid sample
US54478376 févr. 19895 sept. 1995Calypte, Inc.Multi-immunoassay diagnostic system for antigens or antibodies or both
US545336019 mai 199426 sept. 1995Lifescan, Inc.Oxidative coupling dye for spectrophotometric quantitive analysis of analytes
US546836630 sept. 199421 nov. 1995Andcare, Inc.Colloidal-gold electrosensor measuring device
US546984627 sept. 199428 nov. 1995Duquesne University Of The Holy GhostImplantable non-enzymatic electrochemical glucose sensor
US54705339 nov. 199328 nov. 1995Shindo; IsaoTest strip supply apparatus and analyzer using same
US547732630 juin 199419 déc. 1995Bayer CorporationSpectrophotometer arrangement with multi-detector readhead
US548941422 avr. 19946 févr. 1996Boehringer Mannheim, GmbhSystem for analyzing compounds contained in liquid samples
US549463823 sept. 199427 févr. 1996Hypoguard (Uk) LimitedSupport membrane
US550035029 avr. 199419 mars 1996Celltech LimitedBinding assay device
US550239621 sept. 199426 mars 1996Asulab S.A.Measuring device with connection for a removable sensor
US550401121 oct. 19942 avr. 1996International Technidyne CorporationPortable test apparatus and associated method of performing a blood coagulation test
US550817121 févr. 199416 avr. 1996Boehringer Mannheim CorporationAssay method with enzyme electrode system
US550820019 oct. 199216 avr. 1996Tiffany; ThomasMethod and apparatus for conducting multiple chemical assays
US55082036 août 199316 avr. 1996Fuller; Milton E.Apparatus and method for radio frequency spectroscopy using spectral analysis
US550941027 juil. 199423 avr. 1996Medisense, Inc.Strip electrode including screen printing of a single layer
US551215919 août 199430 avr. 1996Matsushita Electric Industrial Co. Ltd.Biosensor
US551584723 mai 199414 mai 1996Optiscan, Inc.Self-emission noninvasive infrared spectrophotometer
US55207866 juin 199528 mai 1996Bayer CorporationMediators suitable for the electrochemical regeneration of NADH, NADPH or analogs thereof
US552611131 août 199311 juin 1996Boehringer Mannheim CorporationMethod and apparatus for calculating a coagulation characteristic of a sample of blood a blood fraction or a control
US55261208 sept. 199411 juin 1996Lifescan, Inc.Test strip with an asymmetrical end insuring correct insertion for measuring
US552680820 avr. 199518 juin 1996Microcor, Inc.Method and apparatus for noninvasively determining hematocrit
US553212812 déc. 19942 juil. 1996Houston Advanced Research CenterMulti-site detection apparatus
US555211617 avr. 19953 sept. 1996Bayer CorporationTest strip pick-up mechanism in automated analyzer
US555426911 avr. 199510 sept. 1996Gas Research InstituteNox sensor using electrochemical reactions and differential pulse voltammetry (DPV)
US55545317 août 199510 sept. 1996Avocet Medical, Inc.Device for performing timed assay by electrical resistance change
US55567891 juil. 199417 sept. 1996Boehringer Mannheim GmbhDevice for the simultaneous determination of several analytes
US55630318 sept. 19948 oct. 1996Lifescan, Inc.Highly stable oxidative coupling dye for spectrophotometric determination of analytes
US556304221 mars 19958 oct. 1996Lifescan, Inc.Whole blood glucose test strip
US556959121 juil. 199429 oct. 1996University College Of Wales AberystwythAnalytical or monitoring apparatus and method
US556960830 janv. 199529 oct. 1996Bayer CorporationQuantitative detection of analytes on immunochromatographic strips
US557215914 nov. 19945 nov. 1996Nexgen, Inc.Voltage-controlled delay element with programmable delay
US557540313 janv. 199519 nov. 1996Bayer CorporationDispensing instrument for fluid monitoring sensors
US557589530 mai 199519 nov. 1996Matsushita Electric Industrial Co., Ltd.Biosensor and method for producing the same
US557607321 avr. 199519 nov. 1996Lpkf Cad/Cam Systeme GmbhMethod for patterned metallization of a substrate surface
US558079431 mai 19953 déc. 1996Metrika Laboratories, Inc.Disposable electronic assay device
US558904531 oct. 199431 déc. 1996Kyoto Daiichi Kagaku Co., Ltd.Data managing method in portable blood sugar value-measuring and portable blood sugar value-measuring apparatus using same
US558932630 déc. 199331 déc. 1996Boehringer Mannheim CorporationOsmium-containing redox mediator
US559339028 févr. 199514 janv. 1997Visionary Medical Products, Inc.Medication delivery device with a microprocessor and characteristic monitor
US559373914 févr. 199614 janv. 1997Lpkf Cad/Cam Systeme GmbhMethod of patterned metallization of substrate surfaces
US55949067 juil. 199414 janv. 1997Boehringer Mannheim CorporationZero power receive detector for serial data interface
US559753220 oct. 199428 janv. 1997Connolly; JamesApparatus for determining substances contained in a body fluid
US56038207 juin 199518 févr. 1997The United States Of America As Represented By The Department Of Health And Human ServicesNitric oxide sensor
US56041107 juin 199518 févr. 1997Celltech Therapeutics Ltd.Binding assay device
US56056621 nov. 199325 févr. 1997Nanogen, Inc.Active programmable electronic devices for molecular biological analysis and diagnostics
US560583714 févr. 199625 févr. 1997Lifescan, Inc.Control solution for a blood glucose monitor
US56205795 mai 199515 avr. 1997Bayer CorporationApparatus for reduction of bias in amperometric sensors
US56208637 juin 199515 avr. 1997Lifescan, Inc.Blood glucose strip having reduced side reactions
US562089014 mars 199515 avr. 1997The United States Of America As Represented By The Secretary Of AgricultureMonoclonal antibodies to hygromycin B and the method of making the same
US562889027 sept. 199513 mai 1997Medisense, Inc.Electrochemical sensor
US563098614 mars 199520 mai 1997Bayer CorporationDispensing instrument for fluid monitoring sensors
US563536223 mai 19943 juin 1997Becton Dickinson And Co.Assay of blood or other biologic samples for target analytes
US56353643 janv. 19943 juin 1997Abbott LaboratoriesAssay verification control for an automated analytical system
US563967128 mars 199517 juin 1997Biostar, Inc.Methods for optimizing of an optical assay device
US564273416 févr. 19961 juil. 1997Microcor, Inc.Method and apparatus for noninvasively determining hematocrit
US56445016 déc. 19941 juil. 1997Lin; ShengfuMethod of using a computer to collect chemical signals directly
US56457985 juin 19958 juil. 1997Boehringer Mannheim GmbhTest elements in sealed chambers for analyzing compounds contained in liquid samples
US565006118 sept. 199522 juil. 1997The Regents Of The University Of CaliforniaLarge amplitude sinusoidal voltammetry
US565006212 sept. 199522 juil. 1997Matsushita Electric Industrial Co., Ltd.Biosensor, and a method and a device for quantifying a substrate in a sample liquid using the same
US56538639 mai 19965 août 1997Bayer CorporationMethod for reducing bias in amperometric sensors
US56541787 juin 19955 août 1997Isk Biosciences CorporationImmunoassay for tetrachloroisophthalonitrile (chlorothalonil), its derivatives and breakdown products
US56565027 juin 199512 août 1997Diagnostic Chemicals LimitedTest strip holder and method of use
US565844319 juil. 199419 août 1997Matsushita Electric Industrial Co., Ltd.Biosensor and method for producing the same
US56588027 sept. 199519 août 1997Microfab Technologies, Inc.Method and apparatus for making miniaturized diagnostic arrays
US56607916 juin 199626 août 1997Bayer CorporationFluid testing sensor for use in dispensing instrument
US566521525 sept. 19959 sept. 1997Bayer CorporationMethod and apparatus for making predetermined events with a biosensor
US567003121 mai 199423 sept. 1997Fraunhofer-Gesellschaft Zur Angewandten Forschung E.V.Electrochemical sensor
US568288427 juil. 19944 nov. 1997Medisense, Inc.Strip electrode with screen printing
US56866597 juin 199511 nov. 1997Boehringer Mannheim CorporationFluid dose flow and coagulation sensor for medical instrument
US569148630 juil. 199625 nov. 1997Bayer CorporationApparatus and methods for selecting a variable number of test sample aliquots to mix with respective reagents
US569163322 juil. 199325 nov. 1997British Technology Group LimitedMethod of and apparatus for determining a property of a sample
US569562314 juin 19909 déc. 1997Disetronic Licensing AgGlucose measuring device
US569808318 août 199516 déc. 1997Regents Of The University Of CaliforniaChemiresistor urea sensor
US570069530 juin 199423 déc. 1997Zia YassinzadehSample collection and manipulation method
US570435423 juin 19956 janv. 1998Siemens AktiengesellschaftElectrocatalytic glucose sensor
US570824714 févr. 199613 janv. 1998Selfcare, Inc.Disposable glucose test strips, and methods and compositions for making same
US57100116 mars 199520 janv. 1998Medisense, Inc.Mediators to oxidoreductase enzymes
US57106227 juin 199520 janv. 1998Boehringer Mannheim CorporationFluid dose, flow and coagulation sensor for medical instrument
US571966730 juil. 199617 févr. 1998Bayer CorporationApparatus for filtering a laser beam in an analytical instrument
US57208625 avr. 199624 févr. 1998Kyoto Daiichi Kagaku Co., Ltd.Sensor and production method of and measurement method using the same
US57232841 avr. 19963 mars 1998Bayer CorporationControl solution and method for testing the performance of an electrochemical device for determining the concentration of an analyte in blood
US572334527 juin 19953 mars 1998Mochida Pharmaceutical Co., Ltd.Method and device for specific binding assay
US57275486 juin 199517 mars 1998Medisense, Inc.Strip electrode with screen printing
US57280745 déc. 199417 mars 1998Visionary Medical Products, Inc.Pen-type injector with a microprocessor and blood characteristic monitor
US574530830 juil. 199628 avr. 1998Bayer CorporationMethods and apparatus for an optical illuminator assembly and its alignment
US574800226 janv. 19965 mai 1998Phase Dynamics Inc.RF probe for montoring composition of substances
US575595417 janv. 199626 mai 1998Technic, Inc.Method of monitoring constituents in electroless plating baths
US575766610 oct. 199626 mai 1998Boehringer Mannheim GmbhSystem for analyzing compounds contained liquid samples
US57593642 mai 19972 juin 1998Bayer CorporationElectrochemical biosensor
US575979423 déc. 19962 juin 1998Becton Dickins & Co.Assay of blood or other biologic samples for target analytes
US576277030 juin 19959 juin 1998Boehringer Mannheim CorporationElectrochemical biosensor test strip
US577671023 déc. 19967 juil. 1998Becton Dickinson And Co.Assay of blood or other biologic samples for target analytes
US578030411 mars 199614 juil. 1998Lifescan, Inc.Method and apparatus for analyte detection having on-strip standard
US578658420 août 199628 juil. 1998Eli Lilly And CompanyVial and cartridge reading device providing audio feedback for a blood glucose monitoring system
US578883314 août 19964 août 1998California Institute Of TechnologySensors for detecting analytes in fluids
US578925529 juil. 19974 août 1998Lifescan, Inc.Blood glucose strip having reduced sensitivity to hematocrit
US579266815 avr. 199611 août 1998Solid State Farms, Inc.Radio frequency spectral analysis for in-vitro or in-vivo environments
US579803112 mai 199725 août 1998Bayer CorporationElectrochemical biosensor
US580105722 mars 19961 sept. 1998Smart; Wilson H.Microsampling device and method of construction
US58073752 nov. 199515 sept. 1998Elan Medical Technologies LimitedAnalyte-controlled liquid delivery device and analyte monitor
US58205516 juin 199513 oct. 1998Hill; Hugh Allen OliverStrip electrode with screen printing
US582066223 juil. 199713 oct. 1998Taisei Dental Mfg. Co., Ltd.Dental investing material
US58329217 nov. 199510 nov. 1998Boehringer Mannheim CorporationAnalog heater control for medical instrument
US583421711 déc. 199610 nov. 1998Becton Dickinson And Co.Assay of blood or other biologic samples for target analytes
US58375467 juin 199617 nov. 1998Metrika, Inc.Electronic assay device and method
US584369131 déc. 19961 déc. 1998Lifescan, Inc.Visually-readable reagent test strip
US584369230 sept. 19971 déc. 1998Lifescan, Inc.Automatic initiation of a time interval for measuring glucose concentration in a sample of whole blood
US584679427 mai 19978 déc. 1998Roquette FreresProcess for the preparation of D-arabitol
US58491741 août 199515 déc. 1998Medisense, Inc.Electrodes and their use in analysis
US585619530 oct. 19965 janv. 1999Bayer CorporationMethod and apparatus for calibrating a sensor element
US585869113 juin 199612 janv. 1999Boehringer Mannheim GmbhMethod and agent for the simultaneous colorimetric and electrochemical measurement of an analyte
US586340012 avr. 199526 janv. 1999Usf Filtration & Separations Group Inc.Electrochemical cells
US58659729 déc. 19962 févr. 1999Universite De GeneveIntegrated electrochemical microsensors and microsystems for direct reliable chemical analysis of compounds in complex aqueous solutions
US587399021 août 199623 févr. 1999Andcare, Inc.Handheld electromonitor device
US587404630 oct. 199623 févr. 1999Raytheon CompanyBiological warfare agent sensor system employing ruthenium-terminated oligonucleotides complementary to target live agent DNA sequences
US588337830 juil. 199616 mars 1999Bayer CorporationApparatus and methods for transmitting electrical signals indicative of optical interactions between a light beam and a flowing suspension of particles
US588583915 avr. 199723 mars 1999Lxn CorporationMethods of determining initiation and variable end points for measuring a chemical reaction
US589048930 juil. 19966 avr. 1999Dermal Therapy (Barbados) Inc.Method for non-invasive determination of glucose in body fluids
US590489817 mars 199818 mai 1999Lre Technology Partner GmbhTest strip
US591187214 oct. 199715 juin 1999California Institute Of TechnologySensors for detecting analytes in fluids
US59161567 févr. 199729 juin 1999Bayer AktiengesellschaftElectrochemical sensors having improved selectivity and enhanced sensitivity
US592192530 mai 199713 juil. 1999Ndm, Inc.Biomedical electrode having a disposable electrode and a reusable leadwire adapter that interfaces with a standard leadwire connector
US592253015 déc. 199513 juil. 1999Lifescan, Inc.Stable coupling dye for photometric determination of analytes
US592259127 juin 199613 juil. 1999Affymetrix, Inc.Integrated nucleic acid diagnostic device
US592502124 juil. 199720 juil. 1999Visionary Medical Products, Inc.Medication delivery device with a microprocessor and characteristic monitor
US59421027 mai 199724 août 1999Usf Filtration And Separations Group Inc.Electrochemical method
US594534121 oct. 199631 août 1999Bayer CorporationSystem for the optical identification of coding on a diagnostic test strip
US594828925 nov. 19967 sept. 1999Matsushita Electric Industrial Co., Ltd.Laser beam machining method
US595819912 mars 199728 sept. 1999Matsushita Electric Industrial Co., Ltd.Biosensor
US596538012 janv. 199912 oct. 1999E. Heller & CompanySubcutaneous glucose electrode
US59687607 nov. 199719 oct. 1999Lifescan, Inc.Temperature-Independent Blood Glucose Measurement
US597192331 déc. 199726 oct. 1999Acuson CorporationUltrasound system and method for interfacing with peripherals
US598991713 févr. 199623 nov. 1999Selfcare, Inc.Glucose monitor and test strip containers for use in same
US600123930 sept. 199814 déc. 1999Mercury Diagnostics, Inc.Membrane based electrochemical test device and related methods
US600444110 juil. 199721 déc. 1999Matsushita Electric Industrial Co., Ltd.Biosensor
US600444217 oct. 199521 déc. 1999Institut Fur Chemo- Und Biosensorik Munster E.V.Analyte-selective sensor
US601317012 juin 199811 janv. 2000Clinical Micro Sensors, Inc.Detection of analytes using reorganization energy
US60427144 déc. 199728 mars 2000National Science CouncilMethod and chemical sensor for determining concentrations of hydrogen peroxide and its precursor in a liquid
US604428512 nov. 199828 mars 2000Lightouch Medical, Inc.Method for non-invasive measurement of an analyte
US604556723 févr. 19994 avr. 2000Lifescan Inc.Lancing device causing reduced pain
US605403918 août 199725 avr. 2000Shieh; PaulDetermination of glycoprotein and glycosylated hemoglobin in blood
US606112824 août 19989 mai 2000Avocet Medical, Inc.Verification device for optical clinical assay systems
US606901110 déc. 199730 mai 2000Umm Electronics, Inc.Method for determining the application of a sample fluid on an analyte strip using first and second derivatives
US607139115 déc. 19976 juin 2000Nok CorporationEnzyme electrode structure
US608674820 févr. 199811 juil. 2000Cornell Research Foundation, Inc.Liposome enhanced immunoaggregation assay and test device
US608718227 août 199811 juil. 2000Abbott LaboratoriesReagentless analysis of biological samples
US609026822 avr. 199718 juil. 2000Imra Japan KabushikikaishaCO gas sensor and CO gas concentration measuring method
US60919751 avr. 199818 juil. 2000Alza CorporationMinimally invasive detecting device
US61028724 mai 199815 août 2000Pacific Biometrics, Inc.Glucose detector and method
US61030334 mars 199815 août 2000Therasense, Inc.Process for producing an electrochemical biosensor
US61035094 sept. 199715 août 2000Lifescan Inc.Modified glucose dehydrogenase
US611035431 oct. 199729 août 2000University Of WashingtonMicroband electrode arrays
US61206764 juin 199919 sept. 2000Therasense, Inc.Method of using a small volume in vitro analyte sensor
US612100916 juil. 199919 sept. 2000E. Heller & CompanyElectrochemical analyte measurement system
US612105029 août 199719 sept. 2000Han; Chi-Neng ArthurAnalyte detection systems
US612660923 nov. 19983 oct. 2000Keith & Rumph Inventors, Inc.Apparatus for taking blood samples from a patient
US612851916 déc. 19983 oct. 2000Pepex Biomedical, LlcSystem and method for measuring a bioanalyte such as lactate
US61298235 sept. 199710 oct. 2000Abbott LaboratoriesLow volume electrochemical sensor
US61344614 mars 199817 oct. 2000E. Heller & CompanyElectrochemical analyte
US613654915 oct. 199924 oct. 2000Feistel; Christopher C.systems and methods for performing magnetic chromatography assays
US613661023 nov. 199824 oct. 2000Praxsys Biosystems, Inc.Method and apparatus for performing a lateral flow assay
US614316416 déc. 19987 nov. 2000E. Heller & CompanySmall volume in vitro analyte sensor
US614324719 déc. 19977 nov. 2000Gamera Bioscience Inc.Affinity binding-based system for detecting particulates in a fluid
US614486911 mai 19997 nov. 2000Cygnus, Inc.Monitoring of physiological analytes
US615012420 mai 199921 nov. 2000Umm Electronics, Inc.Method for passively determining the application of a sample fluid on an analyte strip
US61530699 févr. 199528 nov. 2000Tall Oak VenturesApparatus for amperometric Diagnostic analysis
US61560513 nov. 19995 déc. 2000Stat Medical Devices Inc.Lancet having adjustable penetration depth
US615617318 janv. 20005 déc. 2000Nok CorporationEnzyme electrode structure
US615667330 sept. 19985 déc. 2000Infineon Technologies AgProcess for producing a ceramic layer
US615974515 juil. 199912 déc. 2000Cornell Research Foundation, Inc.Interdigitated electrode arrays for liposome-enhanced immunoassay and test device
US61626113 janv. 200019 déc. 2000E. Heller & CompanySubcutaneous glucose electrode
US616263918 déc. 199819 déc. 2000Amira MedicalEmbossed test strip system
US616856317 mars 19992 janv. 2001Health Hero Network, Inc.Remote health monitoring and maintenance system
US616895725 juin 19972 janv. 2001Lifescan, Inc.Diagnostic test strip having on-strip calibration
US617031830 oct. 19989 janv. 2001California Institute Of TechnologyMethods of use for sensor based fluid detection devices
US617442018 mai 199916 janv. 2001Usf Filtration And Separations Group, Inc.Electrochemical cell
US617575230 avr. 199816 janv. 2001Therasense, Inc.Analyte monitoring device and methods of use
US617698826 mai 199723 janv. 2001Manfred KesslerMembrane electrode for measuring the glucose concentration in fluids
US617997915 nov. 199630 janv. 2001Usf Filtration & Separations Group, Inc.Electrochemical cell
US618006222 févr. 199930 janv. 2001Kyoto Daiichi Kagaku Co., Ltd.Device for analyzing a sample
US619387315 juin 199927 févr. 2001Lifescan, Inc.Sample detection to initiate timing of an electrochemical assay
US619704023 févr. 19996 mars 2001Lifescan, Inc.Lancing device having a releasable connector
US620077330 mars 199913 mars 2001Lifescan, Inc.Diagnostics based on tetrazolium compounds
US620160720 août 199913 mars 2001Mit Development CorporationBlood fluid characteristics analysis instrument
US620395214 janv. 199920 mars 20013M Innovative Properties CompanyImaged article on polymeric substrate
US62062822 mars 199927 mars 2001Pyper Products CorporationRF embedded identification device
US620629220 janv. 200027 mars 2001Sihl GmbhSurface-printable RFID-transponders
US62070001 avr. 199927 mars 2001Roche Diagnostics GmbhProcess for the production of analytical devices
US621241720 août 19993 avr. 2001Matsushita Electric Industrial Co., Ltd.Biosensor
US621857127 oct. 199917 avr. 2001Lifescan, Inc.8-(anilino)-1-naphthalenesulfonate analogs
US622507827 juil. 19981 mai 2001Matsushita Electric Industrial Co., Ltd.Method for quantitative measurement of a substrate
US622608116 mars 19981 mai 2001Optikos CorporationOptical height of fill detection system and associated methods
US623347111 mai 199915 mai 2001Cygnus, Inc.Signal processing for measurement of physiological analysis
US624186212 janv. 19995 juin 2001Inverness Medical Technology, Inc.Disposable test strips with integrated reagent/blood separation layer
US62468623 févr. 199912 juin 2001Motorola, Inc.Sensor controlled user interface for portable communication device
US62469666 avr. 199812 juin 2001Bayer CorporationMethod and apparatus for data management authentication in a clinical analyzer
US625126024 août 199826 juin 2001Therasense, Inc.Potentiometric sensors for analytic determination
US625993719 juin 199810 juil. 2001Alfred E. Mann FoundationImplantable substrate sensor
US626151916 juil. 199917 juil. 2001Lifescan, Inc.Medical diagnostic device with enough-sample indicator
US626274931 déc. 199717 juil. 2001Acuson CorporationUltrasonic system and method for data transfer, storage and/or processing
US626816228 mai 199931 juil. 2001Lifescan, Inc.Reflectance measurement of analyte concentration with automatic initiation of timing
US627063731 août 19997 août 2001Roche Diagnostics CorporationElectrochemical biosensor test strip
US62710446 mai 19987 août 2001University Of Pittsburgh Of The Commonwealth System Of Higher EducationMethod and kit for detecting an analyte
US627236411 mai 19997 août 2001Cygnus, Inc.Method and device for predicting physiological values
US627571723 juin 199814 août 2001Elan Corporation, PlcDevice and method of calibrating and testing a sensor for in vivo measurement of an analyte
US627764117 nov. 199921 août 2001University Of WashingtonMethods for analyzing the presence and concentration of multiple analytes using a diffusion-based chemical sensor
US628100624 août 199828 août 2001Therasense, Inc.Electrochemical affinity assay
US628412519 juin 19964 sept. 2001Usf Filtration And Separations Group, Inc.Electrochemical cell
US628455025 juin 19994 sept. 2001Home Diagnostics, Inc.Diagnostic sanitary test strip
US628759524 mars 200011 sept. 2001Delsys Pharmaceuticals CorporationBiomedical assay device
US629428130 nov. 199825 sept. 2001Therasense, Inc.Biological fuel cell and method
US629478713 août 199825 sept. 2001Heimann Optoelectronics GmbhSensor system and manufacturing process as well as self-testing process
US629550623 oct. 199825 sept. 2001Nokia Mobile Phones LimitedMeasurement apparatus
US62997576 oct. 19999 oct. 2001Therasense, Inc.Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US630012322 oct. 19979 oct. 2001The Victoria University Of ManchesterSensor employing impedance measurements
US630096120 oct. 19999 oct. 2001Acuson CorporationUltrasonic system and method for processing data
US630952626 août 199930 oct. 2001Matsushita Electric Industrial Co., Ltd.Biosensor
US631595120 mai 199913 nov. 2001Lre Technology Partner GmbhTest strip measuring system
US631626417 déc. 199913 nov. 2001Bayer CorporationTest strip for the assay of an analyte in a liquid sample
US632616027 sept. 19994 déc. 2001Cygnus, Inc.Microprocessors for use in a device for predicting physiological values
US632916122 sept. 200011 déc. 2001Therasense, Inc.Subcutaneous glucose electrode
US633046426 août 199911 déc. 2001Sensors For Medicine & ScienceOptical-based sensing devices
US63352038 sept. 19941 janv. 2002Lifescan, Inc.Optically readable strip for analyte detection having on-strip orientation index
US633879021 avr. 199915 janv. 2002Therasense, Inc.Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US63392582 juil. 199915 janv. 2002International Business Machines CorporationLow resistivity tantalum
US634042831 mars 199922 janv. 2002Matsushita Electric Industrial Co., Inc.Device and method for determining the concentration of a substrate
US634236416 nov. 200029 janv. 2002Matsushita Electric Industrial Co., Ltd.Cholesterol sensor and method of determining cholesterol
US634413318 mai 19995 févr. 2002DRäGER SICHERHEITSTECHNIK GMBHProcess for operating an electrochemical measuring cell
US634923025 févr. 199919 févr. 2002Kyoto Daiichi Kagaku Co., Ltd.Blood measuring instrument
US635875220 mai 199919 mars 2002Cornell Research Foundation, Inc.Liposome-enhanced test device and method
US63778965 janv. 199923 avr. 2002Kyoto Daiichi Kagaku Co., Ltd.Method and apparatus for determination of a substance coexisting with another substance
US637951320 sept. 199930 avr. 2002Usf Filtration And Separations Group Inc.Sensor connection means
US638989124 mai 200021 mai 2002Endress + Hauser Gmbh + Co.Method and apparatus for establishing and/or monitoring the filling level of a medium in a container
US639155814 avr. 200021 mai 2002Andcare, Inc.Electrochemical detection of nucleic acid sequences
US639164512 mai 199721 mai 2002Bayer CorporationMethod and apparatus for correcting ambient temperature effect in biosensors
US639495220 avr. 199828 mai 2002Adeza Biomedical CorporationPoint of care diagnostic systems
US639522716 mai 199528 mai 2002Lifescan, Inc.Test strip for measuring analyte concentration over a broad range of sample volume
US64015328 mai 200111 juin 2002Krohne Messtechnik Gmbh & Co. KgFill level gauge
US641341126 oct. 20002 juil. 2002Tall Oak VenturesMethod and apparatus for amperometric diagnostic analysis
US641421330 déc. 19992 juil. 2002Showa Denko K.K.Titanium oxide particle-coated interior member or indoor equipment
US641439517 sept. 19992 juil. 2002Mitsubishi Denki Kabushiki KaishaSemiconductor device capable of preventing disconnection in a through hole
US641441022 juin 20002 juil. 2002Denso CorporationRotary electric machine having reduced winding
US642012812 sept. 200016 juil. 2002Lifescan, Inc.Test strips for detecting the presence of a reduced cofactor in a sample and method for using the same
US644411514 juil. 20003 sept. 2002Lifescan, Inc.Electrochemical method for measuring chemical reaction rates
US64476574 déc. 200010 sept. 2002Roche Diagnostics CorporationBiosensor
US645492123 sept. 199924 sept. 2002Usf Filtration And Separations Group, Inc.Electrochemical cell
US646149627 oct. 19998 oct. 2002Therasense, Inc.Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US64753722 févr. 20005 nov. 2002Lifescan, Inc.Electrochemical methods and devices for use in the determination of hematocrit corrected analyte concentrations
US648404610 juil. 200019 nov. 2002Therasense, Inc.Electrochemical analyte sensor
US64859232 févr. 200026 nov. 2002Lifescan, Inc.Reagent test strip for analyte determination having hemolyzing agent
US648882731 mars 20003 déc. 2002Lifescan, Inc.Capillary flow control in a medical diagnostic device
US648913315 févr. 20013 déc. 2002Lifescan, Inc.Apparatus for determinating the concentration of glucose in whole blood
US649180318 mai 200110 déc. 2002Apex Biotechnology CorporationTest strip and biosensor incorporating with nanometer metal particles
US649187026 nov. 200110 déc. 2002Lifescan, Inc.Optically readable strip for analyte detection having on-strip orientation index
US650197612 juin 200131 déc. 2002Lifescan, Inc.Percutaneous biological fluid sampling and analyte measurement devices and methods
US650338118 sept. 20007 janv. 2003Therasense, Inc.Biosensor
US651298630 déc. 200028 janv. 2003Lifescan, Inc.Method for automated exception-based quality control compliance for point-of-care devices
US651471829 nov. 20014 févr. 2003Therasense, Inc.Subcutaneous glucose electrode
US652111010 nov. 200018 févr. 2003Lifescan, Inc.Electrochemical cell
US652118215 juin 199918 févr. 2003Lifescan, Inc.Fluidic device for medical diagnostics
US652533028 févr. 200125 févr. 2003Home Diagnostics, Inc.Method of strip insertion detection
US652554927 juil. 200025 févr. 2003Lre Technology Partner GmbhMethod for determining the concentration of a substance in a liquid by measuring electrical current in a test strip
US652629820 oct. 200025 févr. 2003Abbott LaboratoriesMethod for the non-invasive determination of analytes in a selected volume of tissue
US65310408 déc. 200011 mars 2003Bayer CorporationElectrochemical-sensor design
US653123924 sept. 200111 mars 2003Therasense, Inc.Biological fuel cell and methods
US653132227 nov. 200011 mars 2003Lifescan, Inc.Visual blood glucose test strip
US65374988 juin 199925 mars 2003California Institute Of TechnologyColloidal particles used in sensing arrays
US653759818 janv. 200225 mars 2003Micro-Tender Industries, Inc.Method for tenderizing raw beef
US653873525 févr. 200025 mars 2003Packard Instrument CompanyMethod and apparatus for producing and measuring light and for determining the amounts of analytes in microplate wells
US65408901 nov. 20001 avr. 2003Roche Diagnostics CorporationBiosensor
US65408916 mai 19991 avr. 2003Abbott LaboratoriesTest strip
US654126628 févr. 20011 avr. 2003Home Diagnostics, Inc.Method for determining concentration of an analyte in a test strip
US65444745 janv. 20018 avr. 2003Amira MedicalDevice for determination of an analyte in a body fluid using small sample sizes
US654979625 mai 200115 avr. 2003Lifescan, Inc.Monitoring analyte concentration using minimally invasive devices
US65514946 avr. 200022 avr. 2003Therasense, Inc.Small volume in vitro analyte sensor
US65550615 oct. 200029 avr. 2003Lifescan, Inc.Multi-layer reagent test strip
US655852820 déc. 20006 mai 2003Lifescan, Inc.Electrochemical test strip cards that include an integral dessicant
US65585297 févr. 20006 mai 2003Steris Inc.Electrochemical sensor for the specific detection of peroxyacetic acid in aqueous solutions using pulse amperometric methods
US65604712 janv. 20016 mai 2003Therasense, Inc.Analyte monitoring device and methods of use
US656262528 févr. 200113 mai 2003Home Diagnostics, Inc.Distinguishing test types through spectral analysis
US656550921 sept. 200020 mai 2003Therasense, Inc.Analyte monitoring device and methods of use
US657039029 août 200127 mai 2003Rigaku CorporationMethod for measuring surface leakage current of sample
US657165127 mars 20003 juin 2003Lifescan, Inc.Method of preventing short sampling of a capillary or wicking fill device
US65728221 août 20023 juin 2003Lifescan, Inc.Visual blood glucose test strip
US657442530 oct. 19983 juin 2003Jack L. AronowitzReflectometer
US65761016 oct. 199910 juin 2003Therasense, Inc.Small volume in vitro analyte sensor
US657611719 mai 199910 juin 2003ArkrayMethod and apparatus for electrochemical measurement using statistical technique
US657641619 juin 200110 juin 2003Lifescan, Inc.Analyte measurement device and method of use
US657646118 juin 200110 juin 2003Therasense, Inc.Electrochemical affinity assay
US65796904 oct. 199817 juin 2003Therasense, Inc.Blood analyte monitoring through subcutaneous measurement
US659112527 juin 20008 juil. 2003Therasense, Inc.Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US659274410 mai 200015 juil. 2003Lifescan, Inc.Method of filling an amperometric cell
US659274517 mai 200015 juil. 2003Therasense, Inc.Method of using a small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US659451420 déc. 200115 juil. 2003Cygnus, Inc.Device for monitoring of physiological analytes
US660099714 déc. 200129 juil. 2003Abbott LaboratoriesAnalyte test instrument having improved calibration and communication processes
US660520014 nov. 200012 août 2003Therasense, Inc.Polymeric transition metal complexes and uses thereof
US660520114 nov. 200012 août 2003Therasense, Inc.Transition metal complexes with bidentate ligand having an imidazole ring and sensor constructed therewith
US660765815 nov. 200019 août 2003Therasense, Inc.Integrated lancing and measurement device and analyte measuring methods
US66168194 nov. 19999 sept. 2003Therasense, Inc.Small volume in vitro analyte sensor and methods
US661893415 juin 200016 sept. 2003Therasense, Inc.Method of manufacturing small volume in vitro analyte sensor
US66235015 avr. 200123 sept. 2003Therasense, Inc.Reusable ceramic skin-piercing device
US662705723 déc. 199930 sept. 2003Roche Diagnostic CorporationMicrosphere containing sensor
US663234914 juil. 200014 oct. 2003Lifescan, Inc.Hemoglobin sensor
US663841514 juil. 200028 oct. 2003Lifescan, Inc.Antioxidant sensor
US663871624 août 199828 oct. 2003Therasense, Inc.Rapid amperometric verification of PCR amplification of DNA
US66453596 oct. 200011 nov. 2003Roche Diagnostics CorporationBiosensor
US664536821 déc. 199811 nov. 2003Roche Diagnostics CorporationMeter and method of using the meter for determining the concentration of a component of a fluid
US665462516 juin 200025 nov. 2003Therasense, Inc.Mass transport limited in vivo analyte sensor
US665670230 juin 19992 déc. 2003Matsushita Electric Industrial Co., Ltd.Biosensor containing glucose dehydrogenase
US66768169 mai 200213 janv. 2004Therasense, Inc.Transition metal complexes with (pyridyl)imidazole ligands and sensors using said complexes
US667699528 juin 200213 janv. 2004Lifescan, Inc.Solution striping system
US668926523 mars 200110 févr. 2004Therasense, Inc.Electrochemical analyte sensors using thermostable soybean peroxidase
US668941128 nov. 200110 févr. 2004Lifescan, Inc.Solution striping system
US669938420 sept. 20002 mars 2004Battelle Memorial InstituteCompact electrochemical sensor system and method for field testing for metals in saliva or other fluids
US674974028 déc. 200115 juin 2004Therasense, Inc.Small volume in vitro analyte sensor and methods
US679034129 août 200014 sept. 2004University Of WashingtonMicroband electrode arrays
US682466917 févr. 200030 nov. 2004Motorola, Inc.Protein and peptide sensors using electrical detection methods
US682467029 nov. 200030 nov. 2004Matsushita Electric Industrial Co. Ltd.Sample discriminating method
US684105221 mai 200111 janv. 2005Bayer CorporationElectrochemical-sensor design
US689042110 mai 200210 mai 2005Lifescan, Inc.Electrochemical methods and devices for use in the determination of hematocrit corrected analyte concentrations
US689354525 nov. 200217 mai 2005Therasense, Inc.Biosensor
US694251828 déc. 200113 sept. 2005Therasense, Inc.Small volume in vitro analyte sensor and methods
US70188437 nov. 200128 mars 2006Roche Diagnostics Operations, Inc.Instrument
US712211129 juin 200417 oct. 2006Matsushita Electric Industrial Co., Ltd.Sample discriminating method
US71320412 févr. 20047 nov. 2006Bayer Healthcare LlcMethods of determining the concentration of an analyte in a fluid test sample
US72761464 oct. 20022 oct. 2007Roche Diagnostics Operations, Inc.Electrodes, methods, apparatuses comprising micro-electrode arrays
US72761475 mars 20032 oct. 2007Roche Diagnostics Operations, Inc.Method for determining the concentration of an analyte in a liquid sample using small volume samples and fast test times
US735132315 janv. 20021 avr. 2008Arkray, Inc.Quantitative analyzing method and quantitative analyzer using sensor
US753768423 juil. 200326 mai 2009Arkray, Inc.Sample analyzing method and sample analyzing device
US810547826 janv. 200531 janv. 2012Siemens AktiengesellschaftMethod for measuring the concentration or change in concentration of a redox-active substance and corresponding device
US8147674 *14 nov. 20083 avr. 2012Bayer Healthcare LlcRapid-read gated amperometry
US2001001726923 mars 200130 août 2001Therasense, Inc.Electrochemical analyte sensors using thermostable soybean peroxidase
US200200041068 juin 200110 janv. 2002Johna LeddyMagnetic composites exhibiting distinct flux properties due to gradient interfaces
US2002001282129 juin 200131 janv. 2002University Of Iowa Research FoundationGradient interface magnetic composites and methods therefor
US2002005352328 déc. 20019 mai 2002Therasense, Inc.Small volume in vitro analyte sensor and methods
US2002007921924 août 200127 juin 2002Mingqi ZhaoMicrofluidic chip having integrated electrodes
US2002008158821 déc. 200027 juin 2002Therasense, Inc.Multi-sensor array for electrochemical recognition of nucleotide sequences and methods
US2002008419628 déc. 20014 juil. 2002Therasense, Inc.Small volume in vitro analyte sensor and methods
US2002012514628 nov. 200112 sept. 2002Kwong-Yu ChanMethods and apparatus for the oxidation of glucose molecules
US2002015796726 févr. 200131 oct. 2002Institute Of Ocupational Safety And Health, Council Of Labor Affairs, Executive YuanElectrochemical gaseous chlorine sensor and method for making the same
US2002018044614 mars 20025 déc. 2002The Regents Of The University Of California Office Of Technology TransferOpen circuit potential amperometry and voltammetry
US200300645254 oct. 20023 avr. 2003Liess Martin DieterMeter
US2003011393318 déc. 200119 juin 2003Rasmus JanssonAnalysis of components in liquids
US200301192082 déc. 200226 juin 2003Yoon Hyun ChulElectrochemical immunosensor and kit and method for detecting biochemical anylyte using the sensor
US2003013667324 mai 200224 juil. 2003Denis PilloudAmperometric sensors using synthetic substrates based on modeled active-site chemistry
US2003014816929 avr. 20027 août 2003Yissum Research Development Company Of The Hebrew University Of JerusalemBiosensor carrying redox enzymes
US200301599277 oct. 200228 août 2003California Institute Of TechnologyColloidal particles used in sensing arrays
US2003017573728 févr. 200118 sept. 2003Jurgen SchuleinQuantifying target molecules contained in a liquid
US2003017618329 mars 200218 sept. 2003Therasense, Inc.Blood glucose tracking apparatus and methods
US2003017832215 janv. 200325 sept. 2003Iyengar Sridhar G.Method and apparatus for processing electrochemical signals
US2003019974417 avr. 200323 oct. 2003Therasense, Inc.Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US200302011949 juin 200330 oct. 2003Therasense, Inc.Small volume in vitro analyte sensor
US200302054653 mai 20026 nov. 2003Chang-Dong FengChloramine amperometric sensor
US200302094501 avr. 200313 nov. 2003Mcvey Iain F.Electrochemical sensor for the specific detection of peroxyacetic acid in aqueous solutions using pulse amperometric methods
US200400057164 oct. 20028 janv. 2004Beaty Terry A.Meter
US200400262533 avr. 200312 févr. 2004Johna LeddyMethods for forming magnetically modified electrodes and articles produced thereby
US200400331657 avr. 200319 févr. 2004California Institute Of TechnologySensor arrays for detecting analytes in fluids
US2004004084011 août 20034 mars 2004Therasense, Inc.Transition metal complexes with bidentate ligand having an imidazole ring
US2004005426715 sept. 200318 mars 2004Therasense, Inc.Small volume in vitro analyte sensor
US2004005589828 juil. 200325 mars 2004Adam HellerIntegrated lancing and measurement device and analyte measuring methods
US2004006081812 sept. 20031 avr. 2004Therasense, Inc.Small volume in vitro analyte sensor and methods of making
US2004007215825 févr. 200215 avr. 2004Henkens Robert W.Electrochemical detection of nucleic acid sequences
US2004007447218 sept. 200322 avr. 2004Martin WirthSpray collision nozzle for direct injection engines
US2004007965323 oct. 200229 avr. 2004Karinka Shridhara AlvaBiosensor having improved hematocrit and oxygen biases
US2004009953114 août 200327 mai 2004Rengaswamy SrinivasanMethods and apparatus for electrochemically testing samples for constituents
US2004011868211 déc. 200324 juin 2004Murray George M.Techniques for sensing chloride ions in wet or dry media
US2004014957716 janv. 20035 août 2004Arun KumarEnzyme electrode and process for preparation thereof
US2004015733717 oct. 200312 août 2004Burke David W.System and method for analyte measurement using AC phase angle measurements
US2004015733817 oct. 200312 août 2004Burke David W.System and method for determining a temperature during analyte measurement
US2004015733917 oct. 200312 août 2004Burke David W.System and method for analyte measurement using AC excitation
US2004022413723 janv. 200411 nov. 2004Rogalska Ewa MariaMethod of binding a compound to a sensor surface
US2004022523012 juin 200411 nov. 2004Therasense, Inc.Small volume in vitro analyte sensor and methods
US2004025624817 oct. 200323 déc. 2004Burke David W.System and method for analyte measurement using dose sufficiency electrodes
US2004025918017 oct. 200323 déc. 2004Burke David W.System and method for analyte measurement employing maximum dosing time delay
US2004026051117 oct. 200323 déc. 2004Burke David W.System and method for determining an abused sensor during analyte measurement
US200500091264 juin 200413 janv. 2005Therasense, Inc.Method and apparatus for providing power management in data communication systems
US2005006989210 févr. 200331 mars 2005Iyengar Sridhar G.Method and apparatus for assay of electrochemical properties
US2005016432213 janv. 200528 juil. 2005Therasense, Inc.Small volume in vitro analyte sensor
US200501761531 nov. 200411 août 2005Lifescan, IncElectrochemical methods and devices for use in the determination of hematocrit corrected analyte concentrations
US2007024635711 avr. 200725 oct. 2007Huan-Ping WuConcentration Determination in a Diffusion Barrier Layer
USRE3626812 juil. 199617 août 1999Boehringer Mannheim CorporationMethod and apparatus for amperometric diagnostic analysis
USRE3699113 août 199919 déc. 2000Matsushita Electric Industrial Co., Ltd.Biosensor and method for producing the same
CA2358993C27 oct. 20002 août 2005Therasense, Inc.Small volume in vitro analyte sensor and related methods
CA2423837C27 oct. 200011 sept. 2007Therasense, Inc.Small volume in vitro analyte sensor and methods
CN1322299C12 juin 200220 juin 2007瓦尔特·洛利Method for producing head element for heater, and head element using this method
CN1328156C27 oct. 200525 juil. 2007上海大学Process for preparing powder material of nano oxide
CN1598564B21 déc. 199821 avr. 2010罗赫诊断手术公司Meter
DE4003194A13 févr. 19908 août 1991Boehringer Mannheim GmbhElectrochemical determn. of analytes - using oxido-reductase and substance of being reduced, which is re-oxidised on the electrode
DE4100727C29 janv. 199122 déc. 1994Klein Karl Dittmar DrAnalytisches Verfahren für Enzymelektrodensensoren
DE4318891A17 juin 19938 déc. 1994Mannesmann AgElektrochemisches Gasspurenmeßsystem mit Funktionskontrolle
DE19824629A12 juin 199816 déc. 1999Biotul Bio Instr GmbhBiosensor for in-situ study of reduction-oxidation processes
DE69915850T28 oct. 19995 janv. 2005Therasense, Inc., AlamedaKleinvolumiger in vitro sensor mit diffusionsfähigem oder nichtauswaschbarem redoxvermittler
EP0010375B12 oct. 197920 juil. 1983Xerox CorporationElectrostatographic processing system
EP0034049B15 févr. 19812 janv. 1985EASTMAN KODAK COMPANY (a New Jersey corporation)Test device for analysis of a plurality of analytes
EP0057110B127 janv. 198217 avr. 1985EASTMAN KODAK COMPANY (a New Jersey corporation)Reaction vessel and method for combining liquids and reagents
EP0120715A229 mars 19843 oct. 1984Christopher Paul HyslopOptical measuring cells
EP0121385A123 mars 198410 oct. 1984Cambridge Life Sciences PlcConductimetric bioassay techniques
EP0127958B28 mai 198410 avr. 1996MediSense, Inc.Sensor electrode systems
EP0132790B119 juil. 198418 janv. 1989Boehringer Mannheim GmbhMethod for making a test stripe
EP0164180B215 mars 198530 sept. 1992Unilever PlcDevices for carrying out chemical and clinical tests, and their use
EP0186286B131 oct. 19852 janv. 1991Unilever N.V.Apparatus for use in electrical, e.g. electrochemical, measurement procedures, and its production and use and composite assemblies incorporating the apparatus
EP0206218B116 juin 19866 mars 1991Miles Inc.Electrode for electrochemical sensors
EP0213343B214 juil. 19861 févr. 1995Nova Biomedical CorporationBlood analyzer
EP0215678B117 sept. 19863 mars 1993Children's Hospital Medical CenterImplantable gas-containing biosensor and method for measuring an analyte such as glucose
EP0230472B219 juin 198613 déc. 2000Matsushita Electric Industrial Co., Ltd.Biosensor and method of manufacturing same
EP0241309A310 avr. 19879 mai 1990MediSense, Inc.Measurement of electroactive species in solution
EP0244326B130 avr. 198718 août 1993BIO MERIEUX Société anonyme dite:Method for detecting and/or identifying a biological substance in a liquid medium with the aid of electrical measurements, and apparatus for carrying out this method
EP0255291B123 juil. 198724 juin 1992Unilever PlcMethod and apparatus for electrochemical measurements
EP0287883A12 avr. 198826 oct. 1988Miles Inc.Test strip device with volume metering capillary gap
EP0330517B227 févr. 19895 févr. 1997Solarcare Technologies CorporationMethod, system and devices for the assay and detection of biochemical molecules
EP0354441B11 août 198917 mai 1995Boehringer Mannheim GmbhMethod for the colorimetric determination of analyte using enzymatic oxydation
EP0359531B112 sept. 198914 avr. 1993Minnesota Mining And Manufacturing CompanyCardioplegia administration set
EP0359831B230 mars 198920 juin 2007Matsushita Electric Industrial Co., Ltd.Biosensor and process for its production
EP0383322B115 févr. 19902 mai 1997Fuji Photo Film Co., Ltd.Biochemical analysis apparatus and method for correcting the results of biochemical analyses
EP0417796B113 sept. 199023 nov. 1994Kabushiki Kaisha Toyota Chuo KenkyushoHematocrit measuring instrument
EP0470649B123 juil. 19872 juin 1999Unilever N.V.Method for electrochemical measurements
EP0471986B119 juil. 199118 oct. 1995Matsushita Electric Industrial Co., Ltd.Quantitative analysis method and its system using a disposable sensor
EP0537761B116 oct. 199227 août 1997Matsushita Electric Industrial Co., Ltd.A biosensor and a method for measuring a concentration of a substrate in a sample
EP0546536B110 déc. 199217 sept. 1997Kyoto Daiichi Kagaku Co., Ltd.Biosensor and method of quantitative analysis using the same
EP0546796A18 déc. 199216 juin 1993Ajinomoto Co., Inc.Treatment of Atherosclerosis
EP0628810A316 mai 199415 nov. 1995Mannesmann AgElectrochemical analyser for gas traces with functioning check.
EP0636880B119 juil. 19919 oct. 2002Kyoto Daiichi Kagaku Co., Ltd.Quantitative analyzing apparatus
EP0640832B130 août 19943 nov. 1999Technic, Inc.Electrochemical immunosensor system
EP0651250A229 oct. 19943 mai 1995Kyoto Daiichi Kagaku Co., Ltd.Data managing method in portable blood sugar value-measuring and portable blood sugar value-measuring apparatus using same
EP0732406B110 juil. 199520 oct. 2004Matsushita Electric Industrial Co., Ltd.A method and a device for quantifying a substrate in a sample liquid using a biosensor
EP0732590B19 janv. 199631 mars 2004Bayer CorporationDispensing instrument for fluid monitoring sensors
EP0741186B123 avr. 199617 oct. 2001Bayer CorporationMethod and apparatus for reduction of bias in amperometric sensors
EP0800086B119 mars 19972 janv. 2003Bayer CorporationControl solution and method for testing the performance of an electrochemical device for determining the concentration of an analyte in blood
EP0837320B18 oct. 199729 mars 2006Bayer CorporationSystem for the optical indentification of coding on a diagnostic test strip
EP0840122B117 oct. 19978 sept. 2004Bayer CorporationMethod and apparatus for calibrating a sensor element
EP0851224B118 déc. 199727 mars 2002Matsushita Electric Industrial Co., Ltd.Biosensor with C-shaped counter electrode
EP0859230A19 févr. 199819 août 1998Cranfield UniversityDetection of analytes using electrochemistry
EP0878708B129 avr. 199813 avr. 2005Bayer CorporationElectrochemical Biosensor having a lid
EP0878713B129 avr. 19984 mars 2009Bayer CorporationMethod and apparatus for correcting ambient temperature effect in biosensors
EP0887421B124 juin 199819 mars 2003Lifescan, Inc.Diagnostic test strip having on-strip calibration
EP0894509B130 juil. 199815 déc. 2004Vyteris, Inc.Bonding agent and method of bonding electrode to printed conductive trace for iontophoresis
EP0942278B112 mars 199912 juin 2002Cygnus, Inc.Biosensor, iontophoretic sampling system and methods of use thereof
EP0958495B16 févr. 199813 nov. 2002Therasense, Inc.Small volume in vitro analyte sensor
EP0964059B127 mai 199913 août 2008Matsushita Electric Industrial Co., Ltd.Biosensor comprising a working and a counter electrode, the counter electrode having a base plate with a curved portion
EP1042667B121 déc. 199817 juin 2009Roche Diagnostics Operations, Inc.Meter
EP1119637B28 oct. 19992 nov. 2011Abbott Diabetes Care Inc.Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
EP1279742A123 juil. 200129 janv. 2003Applied NanoSystems B.V.Method of binding a compound to a sensor surface using hydrophobin
EP1411348B116 juil. 200211 nov. 2015ARKRAY, Inc.Implement and device for analysis
ES2184236T3 Titre non disponible
ES2223185T3 Titre non disponible
FR2325920B1 Titre non disponible
GB2295676B Titre non disponible
JP3260739B2 Titre non disponible
JP2000180399A Titre non disponible
JP2001041925A Titre non disponible
JP2004003478A Titre non disponible
JP2004093478A Titre non disponible
JP2004300328A Titre non disponible
JP2005147990A Titre non disponible
JPH1187213A Titre non disponible
JPH02120657A Titre non disponible
JPS62209350A Titre non disponible
WO1981001794A124 déc. 19809 juil. 1981S AshSystem for demand-based administration of insulin
WO1982003729A18 mars 198228 oct. 1982Lo GortonElectrode for the electrochemical regeneration of co-enzyme,a method of making said electrode,and the use thereof
WO1983000926A126 août 198217 mars 1983Clark, StanleyReflectance meter
WO1986000138A112 juin 19853 janv. 1986Unilever PlcDevices for use in chemical test procedures
WO1986002732A131 oct. 19859 mai 1986Unilever PlcApparatus for use in electrical, e.g. electrochemical, measurement procedures, and its production and use, and composite assemblies incorporating the apparatus
WO1990005293A17 nov. 198917 mai 1990Applied Biosystems, Inc.Assayomate
WO1990005910A313 nov. 198922 avr. 2004I Stat CorpWholly microfabricated biosensors and process for the manufacture and use thereof
WO1991009139A114 déc. 199027 juin 1991Boehringer Mannheim CorporationRedox mediator reagent and biosensor
WO1992001928A118 juil. 19916 févr. 1992I-Stat CorporationMethod for analytically utilizing microfabricated sensors during wet-up
WO1992007655A130 oct. 199114 mai 1992Hypoguard (Uk) LimitedCollection and display device
WO1992015704A127 févr. 199217 sept. 1992Boehringer Mannheim CorporationImproved method and reagent for determination of an analyte
WO1992015859A127 févr. 199217 sept. 1992Boehringer Mannheim CorporationApparatus and method for analyzing body fluids
WO1992015861A127 févr. 199217 sept. 1992Boehringer Mannheim CorporationTest strip holding and reading meter
WO1992015950A127 févr. 199217 sept. 1992Boehringer Mannheim CorporationMethod of communicating with microcomputer controlled instruments
WO1992019961A128 avr. 199212 nov. 1992Massachusetts Institute Of TechnologyTwo-terminal voltammetric microsensors
WO1992022669A119 juin 199223 déc. 1992Hypoguard (Uk) LimitedReagent mixtures for glucose assay
WO1993009433A19 nov. 199213 mai 1993Via Medical CorporationElectrochemical measurement system having interference reduction circuit
WO1993021518A116 avr. 199328 oct. 1993Tadeusz MalinskiNitric oxide sensor
WO1993025898A13 juin 199323 déc. 1993Medisense, Inc.Mediators to oxidoreductase enzymes
WO1994003542A129 juil. 199317 févr. 1994Exxon Chemical Patents Inc.Impact modification of polyamides
WO1994012950A119 nov. 19939 juin 1994Boehringer Mannheim CorporationGlucose test data acquisition and management system
WO1994016095A112 janv. 199421 juil. 1994Avocet Medical, Inc.Method, test article, and system for performing assays
WO1994023295A16 avr. 199413 oct. 1994Ecossensors LimitedBiological species detection method and biosensor therefor
WO1994028414A126 mai 19948 déc. 1994Cambridge Life Sciences PlcSensors based on polymer transformation
WO1994029705A113 mai 199422 déc. 1994Boehringer Mannheim CorporationBiosensing meter which detects proper electrode engagement and distinguishes sample and check strips
WO1995003542A126 juil. 19942 févr. 1995Phase Dynamics, Inc.System and method for monitoring substances and reactions
WO1995007050A323 août 199427 avr. 1995Boehringer Mannheim CorpPower supply control for medical instrument
WO1995022597A121 févr. 199524 août 1995Boehringer Mannheim CorporationMethod of making sensor electrodes
WO1995028634A112 avr. 199526 oct. 1995Memtec America CorporationElectrochemical cells
WO1996004398A11 août 199515 févr. 1996Medisense Inc.Electrodes and their use in analysis
WO1996007908A18 sept. 199514 mars 1996Lifescan, Inc.Optically readable strip for analyte detection having on-strip standard
WO1996013707A919 sept. 1996 Apparatus and method for determining substances contained in a body fluid
WO1996014026A127 oct. 199517 mai 1996Elan Medical Technologies LimitedAnalyte-controlled liquid delivery device and analyte monitor
WO1996015454A116 nov. 199523 mai 1996Australian Membrane And Biotechnology Research InstituteDetection device and method
WO1996033403A118 avr. 199624 oct. 1996The Manchester Metropolitan UniversitySensor
WO1997000441A119 juin 19963 janv. 1997Memtec America CorporationElectrochemical cell
WO1997002487A128 juin 199623 janv. 1997Boehringer Mannheim CorporationElectrochemical biosensor test strip
WO1997008544A121 août 19966 mars 1997Andcare, Inc.Handheld electromonitor device
WO1997016726A131 oct. 19969 mai 1997Chiron Diagnostics CorporationPlanar hematocrit sensor incorporating a seven-electrode conductivity measurement cell
WO1997018465A115 nov. 199622 mai 1997Memtec America CorporationElectrochemical method
WO1997029366A110 févr. 199714 août 1997Australian Membrane And Biotechnology Research InstituteEnzyme detection biosensors
WO1997029847A111 févr. 199721 août 1997Selfcare, Inc.Improved glucose monitor and test strip containers for use in same
WO1997030344A111 févr. 199721 août 1997Selfcare, Inc.Disposable test strips for determination of blood analytes, and methods and compositions for making same
WO1997039343A117 avr. 199723 oct. 1997British Nuclear Fuels PlcBiosensors
WO1997042882A116 mai 199720 nov. 1997Mercury Diagnostics, Inc.Methods and apparatus for sampling and analyzing body fluid
WO1997042888A116 mai 199720 nov. 1997Mercury Diagnostics Inc.Blood and interstitial fluid sampling device
WO1997045719A126 mai 19974 déc. 1997Manfred KesslerMembrane electrode for measuring the glucose concentration in fluids
WO1998005424A131 juil. 199712 févr. 1998Caliper Technologies CorporationAnalytical system and method
WO1998019153A122 oct. 19977 mai 1998The Victoria University Of ManchesterSensor employing impedance measurements
WO1998019159A130 oct. 19977 mai 1998Mercury Diagnostics, Inc.Synchronized analyte testing system
WO1998029740A129 déc. 19979 juil. 1998Commissariat A L'energie AtomiqueMicro system for biological analyses and method for making same
WO1998035225A16 févr. 199813 août 1998E. Heller & CompanySmall volume in vitro analyte sensor
WO1998044342A126 mars 19988 oct. 1998Samduck International CorporationMeasuring device with electrodes fabricated on porous membrane substrate in whole
WO1998057159A112 juin 199817 déc. 1998Clinical Micro Sensors, Inc.Electronic methods for the detection of analytes
WO1998058246A318 juin 199818 mars 1999British Nuclear Fuels PlcImprovements in and relating to compounds, sensors and extractants
WO1998058250A311 juin 19981 avr. 1999Elan Corp PlcMethods of calibrating and testing a sensor for in vivo measurement of an analyte and devices for use in such methods
WO1999022227A329 oct. 19988 juil. 1999Yizhu GuoElectroanalytical applications of screen-printable surfactant-induced sol-gel graphite composites
WO1999022230A120 oct. 19986 mai 1999Pacesetter AbMethod and device for determination of concentration
WO1999032881A121 déc. 19981 juil. 1999Roche Diagnostics CorporationMeter
WO1999038003A921 janv. 199921 oct. 1999I Stat CorpMicrofabricated aperture-based sensor
WO1999045375A122 févr. 199910 sept. 1999Therasense, Inc.Process for producing an electrochemical biosensor
WO1999067628A924 juin 19996 avr. 2000Heller E & CoMulti-sensor array for electrochemical recognition of nucleotide sequences and methods
WO2000016089A917 sept. 199917 août 2000Clinical Micro Sensors IncSignal detection techniques for the detection of analytes
WO2000020626A18 oct. 199913 avr. 2000Therasense, Inc.Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
WO2000020855A14 oct. 199913 avr. 2000Cranfield UniversityAnalysis of mixtures
WO2000029540A116 nov. 199925 mai 2000The Procter & Gamble CompanyUltrasonic cleaning compositions
WO2000057011A117 mars 200028 sept. 2000Canimex Inc.Cable failure device for garage doors and the like
WO2001003207A13 juil. 200011 janv. 2001European Organization For Nuclear ResearchA monolithic semiconductor detector
WO2001021827A119 sept. 200029 mars 2001Roche Diagnostics CorporationSmall volume biosensor for continuous analyte monitoring
WO2001033206A12 nov. 200010 mai 2001Advanced Sensor Technologies, Inc.Microscopic combination amperometric and potentiometric sensor
WO2001033216A127 oct. 200010 mai 2001Therasense, Inc.Small volume in vitro analyte sensor and related methods
WO2001056771A330 janv. 200124 janv. 2002Walter SchmidtMethod for fabricating micro-structures with various surface properties in multilayer body by plasma etching
WO2001057510A325 janv. 200121 févr. 2002Lifescan IncElectrochemical methods and devices for use in the determination of hematocrit corrected analyte concentrations
WO2001057513A37 févr. 20017 févr. 2002Steris IncElectrochemical sensor for the specific detection of peracetic acid in aqueous solutions using pulse amperometric methods
WO2001065246A128 févr. 20017 sept. 2001november Aktiengesellschaft Gesellschaft für Molekulare MedizinQuantifying target molecules contained in a liquid
WO2001067099A17 mars 200113 sept. 2001Inverness Medical LimitedMeasurement of substances in liquids
WO2002031481A22 oct. 200118 avr. 2002Nanogen, Inc.Device and method for electrically accelerated immobilisation and detection of molecules
WO2002031482A32 oct. 20016 sept. 2002Aventis Res & Tech Gmbh & CoDevice and method for electrically accelerated immobilisation of molecules
WO2002077633A113 mars 20023 oct. 2002The Regents Of The University Of CaliforniaOpen circuit potential amperometry and voltammetry
WO2003001195A126 juin 20023 janv. 2003Zellweger Analytics LimitedMonitoring of gas sensors
WO2003066554A13 févr. 200314 août 2003General Electric CompanyProcess and catalyst for purifying phenol
WO2003069304A310 févr. 200324 déc. 2003Agamatrix IncMethod and apparatus for assay of electrochemical properties
WO2003087802A328 mars 20037 oct. 2004Electrochemical Sensor TechnolElectrochemical sensor system and sensing method
WO2004023128A14 sept. 200318 mars 2004Unisearch LimitedDetection of target nucleic acid molecules by alteration of reaction of a redox species following hybridization with immoblized capture nucleic acid molecules
WO2004046707A118 nov. 20033 juin 2004Advanced Sensor TechnologiesMicroscopic multi-site sensor array with integrated control and analysis circuitry
WO2004053476A18 déc. 200324 juin 2004Otre AbSimplified signal processing method for voltammetry
WO2004062801A114 janv. 200429 juil. 2004Diagnoswiss S.A.Multi-layered electrochemical microfluidic sensor comprising reagent on porous layer
WO2004113896A318 juin 200417 févr. 2005Roche Diagnostics GmbhSystem and method for analysis of a biological fluid by the use electrical means
WO2004113912A818 juin 200410 mars 2005Roche Diagnostics GmbhSystem and method for determining a temperature during analysis of biological fluid
WO2004113913A118 juin 200429 déc. 2004Roche Diagnostics GmbhMethod for analyte measurement employing maximum dosing time delay
WO2005001462A818 juin 200417 mars 2005Roche Diagnostics GmbhSystem and method for determining an abused sensor during analyte measurement in a biological fluid
WO2005001463A128 juin 20046 janv. 2005Cranfield UniversityVoltammetric detection of metabolites in physiological fluids
WO2005003748A118 juin 200413 janv. 2005Roche Diagnostics GmbhSystem and method for glucose and hematocrit measurement using ac phase angle measurements
WO2005008231A118 juin 200427 janv. 2005Roche Diagnostics GmbhSystem and method for analyte measurement of biological fluids using dose sufficiency electrodes
WO2005022143B123 août 200410 nov. 2005Agamatrix IncMethod and apparatus for assay of electrochemical properties
WO2006079797A325 janv. 20065 oct. 2006Melys Diagnostics LtdApparatus for measurement of analyte concentration
Citations hors brevets
Référence
1Dalrymple, et al., "Peak Shapes in Semidifferential Electroanalysis", Aug. 9, 1977, pp. 1390-1394, vol. 49, No. 9.
2Gunasingham, et al., "Pulsed amperometric detection of glucose using a mediated enzyme electrode", "Journal of Electroanalytical Chemisty", 1990, pp. 349-362, vol. 287, No. 2.
3International Searching Authority, "International Search Report and Written Opinion for PCT/US2006/028013", Dec. 6, 2006, Publisher: European Patent Office, Published in: EP.
4Parkes, et al., "Balancing Test Time with accurancy and Percision in blood glucose monitoring How fast is too fast?", Jun. 2003.
5Patent Office of the Russian Federation, "Official Action", Jun. 3, 2010, Published in: Russian Federation.
6WIPO, "Search Report and Written Opinion for SG 200800290-9", Feb. 10, 2009, Publisher: Intellectual Property Office of Singapore, Published in: Singapore.
7Yao, et al., "A Thin-Film Glucose Electrode System with Compensation for Drifit", 1989, pp. 742-744, vol. XXXV.
8Yao, et al., "The Low-Potenetail Approach of Glucose Sensing", 1986, pp. 139-146, vol. BME-33, No. 2.
Classifications
Classification aux États-Unis205/777.5, 204/406, 205/792
Classification internationaleA61B5/145, G01N27/26, A61B5/1486, C12Q1/26, G01N27/327, C12Q1/00
Classification coopérativeC12Q1/26, C12Q1/006, A61B5/1486, G01N27/26, A61B5/14546, A61B5/14532, G01N27/3273, A61B2562/0295
Événements juridiques
DateCodeÉvénementDescription
14 janv. 2014ASAssignment
Owner name: BAYER HEALTHCARE LLC, NEW JERSEY
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:WU, HUAN-PING;NELSON, CHRISTINE;BEER, GREG;SIGNING DATESFROM 20071115 TO 20071126;REEL/FRAME:031964/0106
30 juin 2015CCCertificate of correction
23 févr. 2016ASAssignment
Owner name: ASCENSIA DIABETES CARE HOLDINGS AG, SWITZERLAND
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:BAYER HEALTHCARE LLC;REEL/FRAME:037880/0604
Effective date: 20160104